Background and PurposeFrom a physiological perspective, physical activity might be expected to decrease the risk of developing stroke. However, epidemiological studies of physical activity and stroke risk have yielded divergent findings. We therefore sought to examine the association between exercise and stroke risk.MethodsThis was a prospective cohort study of 21 823 men, followed up for an average of 11.1 years. Participants were from the Physicians' Health Study, a randomized trial of low-dose aspirin and beta carotene. Men, aged 40 to 84 years at baseline, were free of self-reported myocardial infarction, stroke, transient ischemic attack, and cancer. At baseline, they reported on the frequency of exercise vigorous enough to work up a sweat. Stroke occurrence was reported by participants and confirmed after medical record review (n=533). We used Cox proportional hazards regression to analyze the data.Resultsor=to5 times per week at baseline were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.61 to 1.03), 0.80 (95% CI, 0.65 to 0.99), and 0.79 (95% CI, 0.61 to 1.03), respectively; P for trend=0.04. In subgroup analyses, the inverse association appeared stronger with hemorrhagic than ischemic stroke. When we additionally adjusted for body mass index, history of hypertension, high cholesterol, and diabetes mellitus, corresponding relative risks for total stroke were 1.00 (referent), 0.81 (95% CI, 0.61 to 1.07), 0.88 (95% CI, 0.70 to 1.10), and 0.86 (95% CI, 0.65 to 1.13), respectively; P for trend=0.25.ConclusionsExercise vigorous enough to work up a sweat is associated with decreased stroke risk in men. In the present study, the inverse association with physical activity appeared to be mediated through beneficial effects on body weight, blood pressure, serum cholesterol, and glucose tolerance. Apart from its favorable influences on these variables, physical activity had no significant residual association with stroke incidence. (Stroke. 1999;30:1-6.)