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The purpose of this study was to examine the reliability and validity of the Short Form (SF)-12 and to determine its ability to detect changes in health related quality of life (HRQOL) following stroke. The study involved a cohort of 90 patients admitted with an ischemic stroke to a hospital in the northeastern United States. The items of the SF-12 were found to be reliable (alpha=0.833–0.894) and to load on a physical and mental component. Three months post-stroke the physical component summary (PCS) scores of the SF-12 were significantly less than population norms. The PCS scores were also lower after stroke (3 month=42.5, 12 month=46.3) than before stroke (48.8). Mental component summary (MCS) scores did not differ significantly from population norms or across time (range=53.6 to 54.9). We conclude that the reliability and validity of the SF-12, as well as its brevity and capacity to document changes in the physical component of HRQOL, provide support for its use in patients with stroke.