The authors used prospective data from two supplemental studies of the National Health Interview Survey, the 1988 Alcohol Supplement and the 1990 Health Promotion and Disease Prevention Supplement, to examine the relation between alcohol intake and mortality. Their study included 17,821 men and 25,874 women aged 40 years or older at baseline; during an average of 6 years of follow-up, 5,540 deaths occurred. The alcohol-mortality relation was U-shaped for men and J-shaped for women. On the basis of categorical analyses adjusted for age, race, smoking, and baseline diseases, men who drank 2 drinks per day had a significantly lower risk of death compared with abstainers (relative risk = 0.60, 95% confidence interval (CI): 0.45, 0.82). The relative risk was 0.75 (95% CI: 0.55, 1.03) after further adjustment for marital status, education, and self-perceived health status. For women, the corresponding relative risks were 0.69 (95% CI: 0.61, 0.78) and 0.79 (95% CI: 0.70, 0.90) for those who drank less than 1 drink per day. When drinking category was considered as an ordinal variable and fitted with a quadratic function in the Cox model, the estimated optimal alcohol intake was approximately less than 1 to 1 drink per day for men and lifetime infrequent to less than 1 drink per day for women. Data from these representative US cohorts demonstrated that less than 2 drinks per day for men and less than 1 drink per day for women are associated with the lowest all-cause mortality.