<h3>Objective:</h3> To examine the efficacy and safety of erenumab, fremanezumab, and galcanezumab, the three self-administered anti-calcitonin gene related peptide monoclonal antibodies (anti-CGRP mAbs) for the treatment of high episodic and chronic migraine (CM) in the largest real-life cohort, to our knowledge. <h3>Background:</h3> Migraine is the most disabling neurological condition and can severely impact activities of daily living. There are few preventative medications with high efficacy for migraine patients. Anti-CGRP mAbs have shown promising results in terms of the severity and frequency of monthly migraine days (MMD), since its first FDA-approval in 2018. Examining real-life cohorts is necessary to confirm the efficacy and tolerability of these treatments. <h3>Design/Methods:</h3> Clinical and demographic data was extracted for patients (n=3421) whom received a minimum of 6 consecutive months of a single anti-CGRP mAb between June 2018 and December 2021. The MMD at baseline and after treatment was recorded. The cohort (85.6% female, 47.2 ± 13.8 years old, 80.3% CM) was separated into response types based on the change in their migraine frequency: “Super-responders” (≥75% MMD reduction), “Non-responders” (≤25% reduction in MMD), and “Responders” (reduction between 26–74%). <h3>Results:</h3> Treatment improved migraine frequency by 48.8% on average. The MMD decreased from a baseline of 21.9 (± 8.1) to 11.3 (± 10.3) after treatment. Super-responders accounted for 32.5% (1113/3421), Responders made up 37.0% (1265/3421), and 30.5% (1043/3421) were Non-responders. No treatment-emergent adverse events were noted, however, adverse reactions occurred in 4.2% (119/3421) of patients. <h3>Conclusions:</h3> Most anti-CGRP mAb treated patients had a positive response, determined by a reduction in MMD. Adverse reactions to the anti-CGRP mAbs occurred rarely in this cohort. Thus, the efficacious and safe use of erenumab, fremanezumab, and galcanezumab is observed in this real-life retrospective study. <b>Disclosure:</b> Miss Salim has nothing to disclose. Mr. Najjar has nothing to disclose. Dr. Ahmed has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie. Dr. Ahmed has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biohaven. Ignacio Mata has nothing to disclose.