Migraine has an impact on health-related quality of life during and between attacks. To improve the quality of life, independent predictors should be identified and managed. A cross-sectional and multivariate analytic study was conducted with adult patients with migraine who first visited the Chulalongkorn Comprehensive Headache Center, King Chulalongkorn Memorial Hospital, Thailand. All information was gathered from patient record forms that were created for and applied to this center. The Thai-version of the Migraine-Specific Quality of Life Questionnaire version 2.1 was used to measure quality of life and tested to discover its independent predictors. Multiple linear regression analysis was used to estimate the sample size. Of 150 consecutive patients screened, 92 had migraines and were recruited for evaluation of independent predictors. The mean age was 39.8 years and 86% were female. The mean duration of the history of migraine was 5.6 years and migraines without aura accounted for 76%. Common independent predictors of the overall quality of life score and scores of the three dimensions of the Thai- version of the Migraine-Specific Quality of Life Questionnaire version 2.1 including role function- restrictive, role function-preventive and emotional function were moderate headache pain intensity and associated symptoms of phonophobia. Stress precipitation was an independent predictor of the overall quality of life score and scores of the role function-preventive and emotional function dimensions. To improve quality of life, adequate treatment during attacks is essential to control headache pain intensity, associated symptoms, especially phonophobia, and then stress management.