<h3>Objective:</h3> Effectiveness and tolerability of brivaracetam (BRV) in routine practice were assessed in a large international population (United States/Europe/Australia). <h3>Background:</h3> To date, real-world evidence studies of BRV have been restricted in scope, location, and numbers, limiting identification of trends in BRV response and tolerability. <h3>Design/Methods:</h3> EXPERIENCE/EPD332 is a meta-analysis of patient-level data from patients with epilepsy initiating BRV in clinical practice. Effectiveness and tolerability outcomes were assessed at 3/6/12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Subgroup analyses were performed by number of prior antiseizure medications (ASMs). <h3>Results:</h3> Analyses included 1644 adults; 92.2%/7.7% had focal-onset/generalized-onset seizures at baseline (mean: 5.5 prior ASMs at baseline [n=1620], 2.1 concomitant ASMs at index [n=1644]). Median BRV duration: 345.5 days (Q1–Q3, 131.5–410.9; n=1629); median dose at index: 100 mg/day (Q1–Q3, 50.0–100.0; n=1615). ≥50% seizure reduction from baseline at 3/6/12 months: 32.1%/36.7%/36.9% (n=619/867/822); seizure freedom (SF; no seizures within 3 months before timepoint): 22.4%/17.9%/14.9% (n=923/1165/1111); continuous SF after baseline (CSF; no seizures reported for any timepoint after baseline): 22.4%/15.7%/11.7% (n=923/1165/1111). Treatment-emergent adverse events (TEAEs) since prior visit: 25.6%/14.2%/9.3% of patients at 3/6/12 months (n=1542/1376/1232). At 12 months, somnolence was the most common TEAE (2.2%). Of patients with TEAEs at 3/6/12 months, 6.4%/2.6%/2.6% had psychiatric TEAEs and 1.6%/0.8%/0.6% had behavioral TEAEs. During follow-up, 551/1639 (33.6%) patients discontinued BRV. In analyses by number of prior ASMs (n=1620; 0–1/2–3/4–6/≥7 ASMs: 15.4%/21.9%/28.8%/34.0%), ≥50% seizure reduction from baseline generally declined with increasing number of prior ASMs at 3 (48.3%–23.1%), 6 (48.0%–26.5%), and 12 months (45.9%–29.9%), as did SF/CSF. In 0–1/2–3/4–6/≥7 ASMs subgroups, TEAE incidences at 12 months were 7.0%/7.4%/11.5%/10.0% (n=214/282/356/359). <h3>Conclusions:</h3> These analyses suggest BRV was effective and well tolerated in highly drug-resistant cohorts. Limitations: challenging to harmonize variables from different studies with mixed populations. <b>Disclosure:</b> Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIAL. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW pharmaceutical. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arvelle. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EISAI. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIAL. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GW pharma. Vicente Villanueva has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Arvelle. Dr. D’Souza has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for LivaNova, Eisai, UCB, Tilray. Dr. D’Souza has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB Pharma, Eisai Pharmaceutical. Dr. D’Souza has stock in Epiminder. The institution of Dr. D’Souza has received research support from UCB Pharma. The institution of Dr. D’Souza has received research support from Eisai Pharmaceutical. Dr. Faught has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurelis. Dr. Faught has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Faught has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Faught has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SK Life Science. Dr. Faught has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for McCaffrey Law Firm. Dr. Faught has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Zulanas Law Firm. Dr. Faught has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Dazio law firm. The institution of Dr. Faught has received research support from UCB Pharma. The institution of Dr. Faught has received research support from UCB Pharma. The institution of Dr. Faught has received research support from NINDS. Dr. Faught has received personal compensation in the range of $500-$4,999 for serving as a Scientific Review Board Member with CDC. Dr. Faught has received personal compensation in the range of $500-$4,999 for serving as a Medicolegal consultant with State of Georgia. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Aquestive. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurelis. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Sience. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eisai. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alliance. The institution of Dr. Klein has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvelle Therapeutics. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Aquestive. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for UCB Pharma. Dr. Klein has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for SK Life Sciences. Dr. Klein has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion. Dr. Klein has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for PrevEp. Dr. Klein has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Fenwick . Dr. Klein has received research support from DOD/CURE. Markus Reuber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Angellini Pharma. Markus Reuber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharma. Markus Reuber has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. The institution of Markus Reuber has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA MedTech. Markus Reuber has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Markus Reuber has received research support from UCB Pharma. Markus Reuber has received publishing royalties from a publication relating to health care. Felix Rosenow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Felix Rosenow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arvelle. Felix Rosenow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharmaceuticals. Felix Rosenow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Felix Rosenow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EISAI. Felix Rosenow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GW Pharmaceuticals. The institution of Felix Rosenow has received research support from EISAI. Felix Rosenow has received publishing royalties from a publication relating to health care. Javier Salas-Puig has nothing to disclose. Dr. Soto Insuga has nothing to disclose. Adam Strzelczyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arvelle Therapeutics. Adam Strzelczyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Desitin Arzneitmittel. Adam Strzelczyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Adam Strzelczyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Marinus. Adam Strzelczyk has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW pharmaceuticals. Adam Strzelczyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UNEEG. Adam Strzelczyk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Adam Strzelczyk has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Zogenix. The institution of Adam Strzelczyk has received research support from GW pharmaceutical. Dr. Szaflarski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for SK Life Sciences. Dr. Szaflarski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for LivaNova Inc. Dr. Szaflarski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Serina Therapeutics. Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Biosciences. An immediate family member of Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Biosciences. Dr. Szaflarski has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Szaflarski has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Law Firm. Dr. Szaflarski has stock in AdCel Biopharma, LLC. Dr. Szaflarski has stock in iFovea. Dr. Besson has received personal compensation for serving as an employee of UCB. Tony Daniels has received personal compensation for serving as an employee of UCB . Tony Daniels has received stock or an ownership interest from UCB. Dr. Floricel has received personal compensation for serving as an employee of UCB Biosciences GmbH. Dr. Floricel has received stock or an ownership interest from UCB Biosciences GmbH. Dr. Laloyaux has received personal compensation for serving as an employee of UCB. Dr. Sendersky has received personal compensation for serving as an employee of UCB. Ms. Zhou has nothing to disclose. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arvelle. Bernhard Steinhoff has received personal compensation in the range of $0-$499 for serving as a Consultant for B.Braun Melsungen. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuraxpharm. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Precisis. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arvelle. Bernhard Steinhoff has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Bernhard Steinhoff has received research support from UCB. The institution of Bernhard Steinhoff has received research support from Eisai. The institution of Bernhard Steinhoff has received research support from SK LIfe Science.