OBJECTIVES: To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. DESIGN: Case-control study. SETTING: A university hospital in Leiden, the Netherlands. PARTICIPANTS: One hundred twenty-one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus. MEASUREMENTS: Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program. Glucose tolerance was assessed according to a 2-hour oral glucose tolerance test. RESULTS: The offspring of nonagenarians siblings had a lower prevalence of metabolic syndrome (P=.03), similar body composition, lower mean fasting blood glucose levels (4.99 vs 5.16 mmol/L; P=.01), lower mean fasting insulin levels (5.81 vs 6.75 mU/L; P=.04), a higher mean homeostasis model assessment of insulin sensitivity (0.78 vs 0.65; P=.02), and a more-favorable glucose tolerance (mean area under the receiver operating characteristic curve for glucose (13.2 vs 14.3; P=.007) than their partners. No significant differences were observed between the offspring and their partners in beta-cell function (insulogenic index 13.6 vs 12.5; P=.38). CONCLUSION: Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.