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This study was designed to assess the long-term efficacy of surgical deactivation of migraine headache trigger sites.One hundred twenty-five volunteers were randomly assigned to the treatment (n = 100) or control group (n = 25) after examination by the team neurologist to ensure a diagnosis of migraine headache. Patients were asked to complete the Medical Outcomes Study 36-Item Short Form Health Survey, Migraine-Specific Quality of Life, and Migraine Disability Assessment questionnaires before treatment and at 12- and 60-month postoperative follow-up. The treatment group received botulinum toxin to confirm the trigger sites; controls received saline injections. Treated patients underwent surgical deactivation of trigger site(s). Results were analyzed at 1 year (previously published) and 5 years postoperatively (the subject of this report).Eighty-nine of 100 patients in the treatment group underwent surgery, and 79 were followed for 5 years. Ten patients underwent deactivation of additional (different) trigger sites during the follow-up period and were not included in the data analysis. The final outcome with or without inclusion of these 10 patients was not statistically different. Sixty-one (88 percent) of 69 patients have experienced a positive response to the surgery after 5 years. Twenty (29 percent) reported complete elimination of migraine headache, 41 (59 percent) noticed a significant decrease, and eight (12 percent) experienced no significant change. When compared with the baseline values, all measured variables at 60 months improved significantly (p < 0.0001).Based on the 5-year follow-up data, there is strong evidence that surgical manipulation of one or more migraine trigger sites can successfully eliminate or reduce the frequency, duration, and intensity of migraine headache in a lasting manner.