OBJECTIVE: This study evaluated the benefit-risk profile of erenumab relative to other therapies approved for migraine prophylaxis and available in the majority of European countries. METHODS: Trials were identified via a published systematic literature review updated to December 2017 using MEDLINE. Erenumab's pivotal trials study reports were also included (NCT02066415, NCT02456740). From these sources,?≥?50% responder rates and discontinuations due to adverse events were extracted to generate numbers needed to treat and harm and likelihood of being helped or harmed, a quantitative benefit-risk measure. RESULTS: Eleven articles (nine randomized clinical trials) met the inclusion/exclusion criteria. Low numbers needed to treat (range: 4-13) were observed for most treatments, while numbers needed to harm showed substantial differences (erenumab's higher numbers needed to harm indicating better tolerability). In chronic and episodic migraine, likelihoods of being helped or harmed for erenumab 70?mg were 143 and 167, and 42 and 167 for erenumab 140?mg. Likelihoods of being helped or harmed in chronic migraine were 2 and 3 for topiramate (two studies) and 4 for onabotulinumtoxinA. In episodic migraine, likelihoods of being helped or harmed were 2 for topiramate and 2 for propranolol. CONCLUSIONS: While all prophylactic treatments were more likely to help than harm (likelihood of being helped or harmed?>?1), erenumab showed a likelihood of being helped or harmed of high magnitude, supporting its favorable benefit-risk profile across the entire migraine frequency spectrum, in contrast with other prophylactic treatments.