BACKGROUND: There is a need to establish which are the more relevant headache-related outcomes that have an impact on our patient's lives to accurately evaluate treatment response in daily clinical practice. OBJECTIVE: The aim of this study was to evaluate the relevance of clinical trial endpoints in clinical real-life disability improvement in response to migraine preventive treatment with OnabotulinumtoxinA. METHODS: This is an observational prospective study. We included patients with chronic migraine fulfilling ICHD-3beta/3 criteria. We prospectively collected data of 8 headache-related and acute medication use endpoints recommended by the Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine. We evaluated their impact on disability improvement after 6 months of treatment with OnabotulinumtoxinA. We defined as a responder in disability, patients with ≥50% MIDAS score reduction after 2 cycles of treatment following PREEMPT protocol. We performed an analysis to measure the impact of improvement in the evaluated outcome measures according to perceived disability in clinical practice. RESULTS: We included 395 patients (85.1% women, mean age 46.7 ± 12.6 years). Mean headache frequency at baseline was 26.5 ± 5.2 headache days/month. After 6 months, 49.1% of patients were headache-related disability responders. From all outcome measures collected, variables independently associated to disability improvement were headache days reduction (p = 0.02) and ≥ 50% pain intensity reduction (p = 0.04). A ≥ 50% reduction in headache frequency or pain intensity showed similar influence on disability improvement after treatment. CONCLUSIONS: Headache pain intensity is as important as frequency when evaluating the clinical response and impact on patient headache-related disability after migraine preventive treatment with OnabotulinumtoxinA.