To investigate whether resistance to activated protein C (APC resistance) because of a mutation in the factor V gene (factor V Leiden) leads to a decrease in life expectancy, we analyzed overall and cause-specific mortality in 171 parents whose offspring carried this mutation. Compared with the Dutch general population, and after adjustment for age, sex, and calendar period, we found no excess deaths in the parents (standardized mortality ratio [SMR], 1.0; 95% confidence interval [CI], 0.8 to 1.2). The cause-specific SMR for malignant neoplasms (1.0; 95% CI, 0.6 to 1.4), diseases of the circulatory system (1.0; 95% CI, 0.7 to 1.4), and cerebrovascular disease (1.0; 95% CI, 0.4 to 1.9) also did not differ from unity. The SMRs for diseases of the respiratory system (1.4; 95% CI, 0.6 to 2.6) and for ischemic heart diseases (1.1; 95% CI, 0.7 to 1.7) were slightly increased. Under the age of 45 years, there was a ninefold increase of dying from ischemic heart disease. Thromboembolic complications were mentioned only once (venous embolism or thrombosis) as an underlying ("primary") cause of death (SMR, 2.3; 95% CI, 0.1 to 13.0) and three times (pulmonary embolisms) as a contributing ("secondary") cause of death (SMR, 1.5; 95% CI, 0.3 to 4.4). We conclude that there is no major effect of APC resistance on life expectancy. Therefore, long-term anticoagulation in carriers of factor V Leiden, on the basis of the carrier state alone, is not indicated.