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To identify predictors of poststroke quality of life.Health-related quality of life (HRQOL) measures assess the impact of disease on the physical, emotional, and social aspects of patients' lives. Although HRQOL measures are used increasingly, factors associated with HRQOL poststroke and the ability of stroke-specific versus generic HRQOL measures to predict patient-reported HRQOL are not well known.A total of 71 patients were evaluated 1 month postischemic stroke with a new stroke-specific HRQOL measure-the SS-QOL-and the SF-36, a generic HRQOL measure. Stroke severity, impairments, and functional limitations were also measured. Demographic variables and outcome measure scores were compared between patients rating their overall HRQOL the same as prestroke versus those with overall HRQOL worse than prestroke. Independent predictors of overall HRQOL were identified using multivariable modeling.Variables associated with better overall HRQOL were higher (better) SS-QOL and Barthel Index scores, and lower (better) NIH Stroke Scale and Beck Depression Inventory scores. Independent predictors of good overall HRQOL were the SS-QOL score (odds ratio [OR], 2.97; 95% CI, 1.3, 7.1; p = 0.01) and NIH Stroke Scale score (OR, 0.69; 95% CI, 0.47, 0.99; p = 0.05). Demographic factors and SF-36 scores were not associated with overall HRQOL ratings.Stroke-specific quality of life score and patient impairments predict patient-reported overall health-related quality of life (HRQOL) poststroke. SF-36 scores were not associated with overall HRQOL ratings. Disease-specific HRQOL measures are more sensitive to meaningful changes in poststroke HRQOL and may thus aid in identifying specific aspects of poststroke function that clinicians and "trialists" can target to improve patients' HRQOL after stroke.