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STUDY OBJECTIVE: To examine the potential for stroke prevention by avoidance of hazards related to lifestyle. Assessment of the lifelong contribution of both individual and combined exposures was a particular feature of the study. An estimate was sought of the proportion (population attributable risk fraction) of strokes likely to be caused by one or a combination of cigarette smoking, lack of exercise, and obesity. DESIGN: Case-control study. SETTING: Eleven general practices in west Birmingham. PARTICIPANTS: Altogether 125 men and women who had just had their first stroke and were aged 35-74 and 198 controls frequency matched for age and sex recruited over 24 months during 1988-90. MAIN RESULTS: The hazards of cigarette smoking for stroke were confirmed and noted to persist for one to two decades after stopping smoking. Cigarette smoking was estimated to have caused 49% (95% confidence level 22, 67%) of the strokes in this population with roughly equal contributions from current and former smoking. Combinations of cigarette smoking (current and former) with lack of exercise or previous obesity apparently caused 62% and 72% of the strokes respectively. If cigarette smoking, lack of exercise and obesity were all avoided, 79% (32, 94%) of the strokes could potentially have been prevented. No stroke patient reported a combination of never smoking, taking regular exercise aged 15 to 25, and avoidance of overweight (body mass index > 25 kg/m2). CONCLUSIONS: Taken together, the combination of cigarette smoking, excessive body fat, and lack of exercise accounted for a major proportion of stroke cases in the population studied. It appears that these easily identifiable factors related to lifestyle are a major and possibly predominant cause of stroke, at least until the age of 75.