When counseling first-degree relatives of patients with venous thromboembolism (VTE), it is important to know whether factors other than thrombophilia influence their risk for thrombosis. We assessed the risk for VTE in 915 first-degree relatives of patients with provoked VTE, compared this with the risk in 1752 first-degree relatives of patients with unprovoked VTE, and then combined data from the 2 groups of relatives to identify predictors of thrombosis. There had been 123 VTEs in 2617 first-degree relatives (0.12 per 100 person-years). The risk for VTE in first-degree relatives was higher if the index cases had an unprovoked compared with a provoked VTE (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.43-3.85), if the index case was younger (OR, 0.97 per year older; 95% CI, 0.96-0.99), and if an additional family member had VTE (OR, 2.71; 95% CI, 2.22-3.31). Among first-degree relatives of an index case with factor V Leiden or the prothrombin 20210A gene variant, the presence of these abnormalities also predicted thrombosis (OR, 4.42; 95% CI, 1.35-14.38). We conclude that thrombosis at a young age and unprovoked VTE predict VTE in first-degree relatives, and that the influence of these 2 factors is additive.