OBJECTIVES: Chronic migraine produces significant societal costs and reductions in quality of life.  OnabotulinumtoxinA is licensed in Canada for the prophylaxis of headaches in adults with chronic migraine. We developed a model to estimate the cost-effectiveness of onabotulinumtoxinA for patients with chronic migraine who are intolerant or refractory to two or more oral prophylaxis agents. METHODS: A state transition model with a three-year time horizon was developed to estimate the incremental impact of onabotulinumtoxinA relative to placebo in units of  quality adjusted life years (QALYS) for adults with chronic migraine in Canada.  Each treatment cohort was divided into health states defined by the number of headache days experienced per month. A societal perspective was taken, including cost of treatment, acute health care resource use, absenteeism, and presenteeism. Pooled data from the subgroup of patients who had previously tried two or more prophylactics in the Phase III clinical trial program were used to estimate the baseline health state distributions and transition probabilities. Quality of life and health care resource utilization were estimated from a large international observational study of migraine patients.   RESULTS: Treatment with onabotulinumtoxinA produced an incremental benefit of 0.151 QALYs over 3 years at an incremental cost of $974 compared to placebo, thus resulting in an Incremental Cost Effectiveness Ratio (ICER) of $6,450/QALY.  Results were most sensitive to hourly wage, mean lost work hours, and mean number of hospitalizations in the three highest headache days per month health states. OnabotulinumtoxinA remains cost-effective when excluding lost productivity costs, with an ICER of $24,504/QALY.  CONCLUSIONS: In this study, onabotulinumtoxinA was shown to be a cost-effective treatment option and may be considered good value for money from a Canadian societal perspective for the prophylaxis of headaches in adults with chronic migraine who fail or are intolerant to other treatment options.