Background: Midlife characteristics have been associated with survival to advanced ages. However, the predictive ability of such indicators to distinguish extreme from above-average longevity remains uncertain. We assessed a variety of potential indicators of exceptional vs. above-average longevity in a cohort of working males. Methods: A nested case-control study was conducted within the Israeli Ischemic Heart Disease (IIHD) cohort (n=10,059), consisting of civil servants and municipal employees recruited in 1963 at ages 40-65 years and followed-up for mortality over 55 years (last follow-up, 2019). All participants who survived to age 95 years or more (n=692) were individually matched (1:3) on year of birth to controls who died at ages 80-94 (n=2,076). Sociodemographic, behavioral, clinical, biochemical, and psychosocial data were obtained in 3 study cycles (1963, 1965, and 1968). Logistic regression models were constructed to identify significant predictors of extreme longevity, with over 500 variables screened. Results: Among participants in the IIHD cohort, 52.1% died before reaching 80 years of age, 41.0% survived to age 80-94 years, and 6.9% survived to age 95 years or more [median (IQR) age at death, 79 (70-87) years]. In the case-control analysis, after removal of highly correlated variables, 10 variables were significantly associated with exceptional (95+) longevity (Table). In a multivariable model, education level, low self-perceived employment difficulties, avoiding heavy smoking, maintaining optimal blood pressure and cholesterol levels, and absence of coronary heart disease were the variables most strongly associated with reaching 95 years of age. Conclusions: Using data from a large cohort of male employees assessed during midlife and followed to end of life, we were able to identify a few sociodemographic, lifestyle, clinical, and psychosocial variables associated with extreme longevity, some of which are genetically mediated.