BACKGROUND: Chronic migraine is a disabling condition, often associated with comorbidities including cognitive dysfunction, anxiety and depression. It is unclear whether cognitive complaints are associated with the underlying migraine pathophysiological process or related to drugs or comorbidities of depression and anxiety. OBJECTIVE: To evaluate cognitive changes in chronic migraine and assess reversibility of cognitive dysfunction following effective migraine treatment using onabotulinumtoxinA. METHODS: This was a prospective real-world study of 60 patients with chronic migraine treated with onabotulinumtoxinA. Headache diaries recorded total headache days at baseline and duration of 12 weeks post-treatment. Computerised cognitive tests of reaction time and working memory (WM) speed and accuracy using a purpose-specific website was implemented at baseline, 6 weeks and 12 weeks. The Patient Health Questionnaire (PHQ-9) and Penn State Worry Questionnaire-Past Week (PSWQ-PW) were administered for depression and anxiety levels. Associations between clinical response, cognitive parameters, PHQ-9 and PSWQ-PW were analysed. RESULTS: At 6 weeks post-treatment, 88% patients achieved good response (50% reduction in headache frequency) with improvement of PHQ-9, PSWQ-PW, cognitive speed tests and WM accuracy compared with baseline (all p<0.05). There was no overall correlation between good headache response and improved cognitive measures and no association between good headache response and improved PHQ-9 and PSWQ-PW scores. Improved WM accuracy correlated with reduced PSWQ-PW (p=0.047). There was no correlation between improved WM accuracy and reduced PHQ-9. CONCLUSIONS: OnabotulinumtoxinA treatment for chronic migraine improved anxiety, depression and cognitive performances but these improvements did not correlate with reduction in headache and migraine frequency. Improved WM accuracy was significantly associated with reduced anxiety level.