In a previous study, sumatriptan therapy was associated with improvements in Health Related Quality of Life (HRQoL). Using the same population, the present study explores additional changes in HRQoL between patients who did and did not receive migraine prophylaxis medication. OBJECTIVES: To compare the difference in HRQoL of migraineurs who did and did not receive migraine prophylactic medication. METHODS: A retrospective database analysis was conducted using pharmacy claims and HRQoL data. Study patients were from a managed care organization, were diagnosed with migraine, and were initiated on sumatriptan (baseline). The SF-36 and Migraine-Specific Quality of Life Questionnaire-Version 1.0 (MSQ) surveys were administered at baseline, 3 and 6 months after initiation of sumatriptan. Patients were identified for the prophylaxis group if they received any medication from a previously developed list of possible migraine prophylaxis medications: 1) within 30 days prior to baseline and 2) at least 4 out of the 6 months after baseline. A two-way repeated measures ANOVA was performed comparing differences in HRQoL between the groups from baseline to 6 months. RESULTS: Of 178 patients, 40 were in the prophylaxis group and 138 in the non-prophylaxis group. Statistically significant increases were found in the MSQ Role Function-Restrictive, and the SF-36 Role-Physical, Bodily Pain domains in the non-prophylaxis group compared with the prophylaxis group (p-value <0.05). A statistically significant increase was found in the SF-36 Physical Functioning domain in the prophylaxis group compared with the non-prophylaxis group (p-value <0.05). CONCLUSION: Although sumatriptan has been shown to improve HRQoL of migraineurs, concurrent use of prophylaxis medication for migraineurs shows mixed results of any additional benefit in HRQoL.