Background and Purpose-Physical activity reduces the risk of premature death and cardiovascular disease, but the relationship to stroke is less well studied. The objective of this study was to investigate the association between leisure-time physical activity and ischemic stroke in an urban, elderly, multiethnic population. Methods-The Northern Manhattan Stroke Study is a population-based incidence and case-control study. Case subjects had first ischemic stroke, and control subjects were derived through random-digit dialing with 1:2 matching for age, sex, and race/ethnicity. Physical activity was recorded through a standardized in-person interview regarding the frequency and duration of 14 activities over the 2 prior weeks. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals after adjustment for medical and socioeconomic confounders. Results-Over 30 months, 369 case subjects and 678 control subjects were enrolled. Mean age was 69.9Ϯ12 years; 57% were women, 18% whites, 30% blacks, and 52% Hispanics. Leisure-time physical activity was significantly protective for stroke after adjustment for cardiac disease, peripheral vascular disease, hypertension, diabetes, smoking, alcohol use, obesity, medical reasons for limited activity, education, and season of enrollment (ORϭ0.37; 95% confidence intervalϭ0.25 to 0.55). The protective effect of physical activity was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. A dose-response relationship was shown for both intensity (light-moderate activity ORϭ0.39; heavy ORϭ0.23) and duration (Ͻ2 h/wk ORϭ0.42; 2 to Ͻ5 h/wk ORϭ0.35; Ն5 h/wk ORϭ0.31) of physical activity. Conclusions-Leisure-time physical activity was related to a decreased occurrence of ischemic stroke in our elderly, multiethnic, urban subjects. More emphasis on physical activity in stroke prevention campaigns is needed among the elderly. (Stroke. 1998;29:380-387.)