Background: Premature cardiovascular disease (CVD) is treated in the same way as CVD of advanced age. However, in patients with premature CVD and a family history of CVD, different -possibly genetic- mechanisms may underlie this disease, which current medical treatment is not targeted to. This suggests that subjects with a genetic predisposition to CVD are more likely to have recurrent cardiovascular events. Methods: We retrospectively investigated 291 patients with premature CVD and assessed the amount of recurrent events according to family history in a follow-up period of 31 years. Premature CVD was defined as an event <51 years for men or <56 for women. We used a Cox proportional hazards model to estimate the relationship between a positive family history and recurrence of cardiovascular events. Results: Patients with recurrent events had more often a positive family history (60.0% vs. 47.1%; p<0.05), were more often smokers (85.2% vs. 70.7%; p<0.05), had more often hypertension (36.3% vs. 23.6%; p<0.05) and had a longer follow-up period (10.0 years vs. 5.4 years; p<0.001) than patients without recurrent events. After adjusting for these differences and modelling time to events, a positive family history was independently associated with recurrent events (Hazard ratio 1.31 (95% confidence intervals (CI) 1.01-1.72; p<0.05)). Conclusions: Patients with a genetic predisposition for CVD are at risk for recurrent events, after adjusting for risk factors and other confounders. This might imply that in subjects with a genetic predisposition for CVD different pathophysiological mechanisms are active, leading to recurrent events.