Many demographic, socioeconomic, and behavioral risk factors predict mortality in the United States. However, very few population-based longitudinal studies are able to investigate simultaneously the impact of a variety of social factors on mortality. We investigated the degree to which demographic characteristics, socioeconomic variables and major health risk factors were associated with mortality in a nationally-representative sample of 3617 U.S. adults from 1986 to 2005, using data from the 4 waves of the Americans' Changing Lives study. Cox proportional hazard models with time-varying covariates were employed to predict all-cause mortality verified through the National Death Index and death certificate review. The results revealed that low educational attainment was not associated with mortality when income and health risk behaviors were included in the model. The association of low income with mortality remained after controlling for major behavioral risks. Compared to those in the "normal" weight category, neither overweight nor obesity was significantly associated with the risk of mortality. Among adults age 55 and older at baseline, the risk of mortality was actually reduced for those were overweight (hazard rate ratio = 0.83) and those who were obese (hazard rate ratio = 0.68), controlling for other health risk behaviors and health status. Having a low level of physical activity was a significant risk factor for mortality (hazard rate ratio = 1.58). The results from this national longitudinal study underscore the need for health policies and clinical interventions focusing on the social and behavioral determinants of health, with a particular focus on income security, smoking prevention/cessation, and physical activity.