OBJECTIVES: To assess whether familial longevity can be attributed to sustained hematopoietic capacity. DESIGN: Prospective follow-up study of two independent population-based cohorts. SETTING: The Leiden Longevity Study and the Leiden 85-plus Study. PARTICIPANTS: From the Leiden Longevity Study, 1,001 nonagenarians with familial longevity were included. As age-matched controls, 260 nonagenarians without familial longevity were used from the Leiden 85-plus Study. MEASUREMENTS: Hemoglobin, leukocytes, and thrombocytes were measured for all subjects with and without familial longevity. Standardized mortality ratios, linear regression, and left-censored Cox regression were used for statistical analysis. RESULTS: Mortality in nonagenarians with familial longevity was 28% lower than in nonagenarians from the general population (standardized mortality ratio=0.72, 95% confidence interval (CI)=0.65-0.79, P<.001). No differences were found between hemoglobin, leukocyte, and thrombocyte count in nonagenarians with and without familial longevity (all P>.30). Nonagenarians with familial longevity had greater mortality risk when anemia was present (sex-adjusted hazard ratio=1.71, 95% CI 1.41-2.07, P<.001). No relationship was found between leukocytes, thrombocytes, and mortality in either study group (all P>.20). CONCLUSION: Hematopoietic capacity cannot explain the significantly better survival of nonagenarians with familial longevity, but in those with familial longevity, anemia may contribute to mortality.