Offspring of parents with exceptional longevity (OPEL) manifest lower prevalence of cardiovascular disease (CVD), but the role of lifestyle factors in this unique cohort is not known. Our study tested whether OPEL have lesser prevalence of CVD independent of lifestyle factors. Prevalence of CVD and CVD risk factors was assessed in a population of community-dwelling Ashkenazi Jewish adults aged 65 to 94 years. Participants included OPEL (n = 395), defined as having at least 1 parent living past the age of 95 years, and offspring of parents with usual survival (OPUS, n = 450), defined as having neither parent survive to 95 years. Medical and lifestyle information was obtained using standardized questionnaires. Socioeconomic status was defined based on validated classification scores. Dietary intake was evaluated with the Block Brief Food Frequency Questionnaire (2000) in a subgroup of the study population (n = 234). Our study found no significant differences in the prevalence of obesity, smoking, alcohol use, physical activity, social strata scores, and dietary intake between the 2 groups. After adjustment for age and gender, the OPEL demonstrated 29% lower odds of having hypertension (95% confidence interval [CI] 0.53 to 0.95), 65% lower odds of having had a stroke (95% CI 0.14 to 0.88), and 35% lower odds of having CVD (95% CI 0.43 to 0.98), compared with OPUS. In conclusion, exceptional parental longevity is associated with lower prevalence of CVD independent of lifestyle, socioeconomic status, and nutrition, thus highlighting the potential role of genetics in disease-free survival among individuals with exceptional parental longevity.