<h3>Objective:</h3> To report safety for the full follow-up and efficacy through 156 weeks of CBD treatment in an OLE (NCT02544750). <h3>Background:</h3> Safety and efficacy of add-on CBD in TSC was demonstrated in a phase 3 randomized controlled trial (RCT; GWPCARE6 [NCT02544763]). <h3>Design/Methods:</h3> Patients who completed GWPCARE6 RCT were enrolled to receive CBD (Epidiolex<sup>®</sup>; 100 mg/mL oral solution), starting dose 25 mg/kg/d with titration up to maximum 50 mg/kg/d. Primary endpoint: safety. Secondary endpoints: percentage change in TSC-associated (countable focal and generalized) seizures, responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC). <h3>Results:</h3> Of 201 RCT completers, 199 (99%) entered OLE. At baseline, median (range) age was 10.7 years (1.1–56.8) and number of ASMs was 3 (0–5). Most common concomitant ASMs were valproate (43%), vigabatrin (37%), and clobazam (35%). Baseline median (Q1, Q3) monthly TSC-associated seizure frequency: 57 (28, 109). Thirty-four patients (17%) completed treatment; most common reason for withdrawal was transition to commercial product (93 [56%]). Median (range) treatment time: 631 days (18–1462). Mean (SD) modal dose: 28 mg/kg/d (9). AEs incidence: 96% of patients, serious AEs incidence: 28%; discontinuation because of an AE: 9%. Most common AEs: diarrhea (47%), seizures (30%), pyrexia (24%), and decreased appetite (24%). Overall, 7% of patients had elevation in ALT levels and 5% in AST levels. There was 1 death due to cardiopulmonary failure, deemed not treatment related. Median percentage reduction in TSC-associated seizures (12-week windows through 156 weeks): 53%–90%. Seizure responder rates (≥50%, ≥75%, and 100%) ranged from 52%–78%, 29%–69%, and 6%–31% across 12-week windows through 156 weeks. Improvements on S/CGIC were reported by 89% and 93% of subjects/caregivers at 52 and 104 weeks. <h3>Conclusions:</h3> Add-on CBD treatment was well tolerated and produced sustained reductions in TSC-associated seizures for up to 156 wks in patients treated in OLE. <b>Disclosure:</b> Dr. Thiele has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GW Pharma. Dr. Thiele has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zogenix. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for West Therapeutics. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for RegenxBio. Dr. Thiele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for nobelpharma. An immediate family member of Dr. Thiele has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Thor labs. Dr. Thiele has received personal compensation in the range of $0-$499 for serving as a Consultant for Biocodex. The institution of Dr. Thiele has received research support from GW Pharma. The institution of Dr. Thiele has received research support from Zogenix. Dr. Bebin has received personal compensation for serving as an employee of GW Pharma. Dr. Bebin has received personal compensation for serving as an employee of Biocodex. Dr. Bebin has received personal compensation for serving as an employee of Regenxbio. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GW Pharma. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biocodex. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regenxbio. The institution of Dr. Bebin has received research support from GW Pharma. The institution of Dr. Bebin has received research support from NINDS. Dr. Filloux has nothing to disclose. Floor Jansen has nothing to disclose. Patrick Kwan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EDUCOM SPA. Patrick Kwan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Patrick Kwan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. The institution of Patrick Kwan has received research support from UCB. The institution of Patrick Kwan has received research support from Eisai. Rachel Loftus has received personal compensation for serving as an employee of Jazz Pharmaceuticals . Rachel Loftus has stock in Jazz Pharmaceuticals Inc . Dr. Sahebkar-Moghaddam has received personal compensation for serving as an employee of gw. Dr. Sahebkar-Moghaddam has stock in GW. Dr. Sparagana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences. Dr. Sparagana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nobelpharma. The institution of Dr. Sparagana has received research support from Greenwich Biosciences. The institution of Dr. Sparagana has received research support from Tuberous Sclerosis Alliance. The institution of Dr. Sparagana has received research support from Novartis. Dr. Sparagana has a non-compensated relationship as a Professional Advisory Board Member, committee member with Tuberous Sclerosis Alliance that is relevant to AAN interests or activities. John Lawson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cerecin. John Lawson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chiesi. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for LivaNova. Dr. Wheless has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Supernus. Dr. Wheless has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Greenwich. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BioMarin. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zogenix. Dr. Wheless has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelius.