To evaluate the longitudinal performance of the migraine-specific quality of life (MSQOL) instrument. Psychometric tests evaluated data obtained from 1383 migraineurs who completed the 20-item MSQOL questionnaire during a noncomparative, long-term, observational study of zolmitriptan (Zomig), 5 mg, for the acute treatment of migraine attacks of any intensity. There was a relationship between a history of a high frequency of migraine attacks and low baseline MSQOL scores, indicating a lower quality of life. Principal components analyses confirmed three domains and an overall score. Cronbach alpha coefficients for the overall score (.93) indicated high internal consistency. Responsiveness analysis over 180 days of treatment indicated a significantly greater improvement in MSQOL scores (P <.05) in treatment responders compared with nonresponders. The average effect size (0.25) and Guyatt responsiveness statistic (0.46) for the MSQOL instrument exceeded those for the eight domains of the Medical Outcomes Study Short Form Health Survey (MOS SF-36) (-0.05 to 0.14 and 0.01 to 0.12, respectively). Change from baseline for responders in MSQOL total score was 4.7 to 5.4 compared with 1.1 to 2.7 for nonresponders. Cumulative evidence for the MSQOL instrument meets established criteria for validity, consistency, and reproducibility and shows moderate responsiveness to treatment. This instrument fulfils the need for an MSQOL measure to be used as an adjuvant measure in the assessment of long-term outcomes of therapy.