Background and Purpose The purpose of this study was to determine the effect of a history of parental death from stroke or heart trouble on the risk of major stroke events (fatal and nonfatal) in middle-aged British men. Methods A prospective study was undertaken of 7735 middle-aged men, drawn at random from general practices in 24 British towns, who were followed up for an average of 14.8 (range, 13.5 to 16.0) years. Results In the 7683 men providing information on at least one of their parents, there were 278 major stroke events and 947 major ischemic heart disease events. A history of death from stroke or heart trouble in mother or father was associated with a significantly increased risk of stroke independent of other risk factors, including hypertension. The association is due almost entirely to an increased risk of nonfatal stroke. In comparison with men whose parents were still alive or who had no history of parental death from either heart trouble or stroke, the adjusted relative risk of stroke in men with a history of parental stroke death was 1.4 (95% confidence interval [CI], 1.1 to 2.0; P =.02), and in men with parental heart trouble death, the relative risk was 1.3 (95% CI, 1.0 to 1.7; P =.04). The positive relationships were present whether the parental death occurred before or after 70 years of age. A parental death from stroke was not associated with increased risk of an ischemic heart disease event, although the latter was significantly associated with a history of parental death from heart trouble. Conclusions Although factors such as hypertension and smoking are of major importance in the etiology of stroke, there is a link between a history of parental death from cardiovascular disease (stroke or heart trouble) and the risk of stroke that appears to be independent of the established risk factors.