The authors investigated the role of self-reported life satisfaction in mortality with a prospective cohort study (1976–1995). A nationwide sample of healthy adults (18–64 years, n = 22,461) from the Finnish Twin Cohort responded to a questionnaire about life satisfaction and known predictors of mortality in 1975. A summary score for life satisfaction (LS), defined as interest in life, happiness, loneliness, and general ease of living (scale range, 4–20), was determined and used as a three-category variable: the satisfied (LS, 4–6) (21%), the intermediate group (LS, 7–11) (65%), and the dissatisfied (LS, 12–20) (14%). Mortality data were analyzed with Cox regression. Dissatisfaction was linearly associated with increased mortality. The age-adjusted hazard ratios of all-cause, disease, or injury mortality among dissatisfied versus satisfied men were 2.11 (95% confidence interval (CI): 1.68, 2.64), 1.83 (95% CI: 1.40, 2.39), and 3.01 (95% CI: 1.94, 4.69), respectively. Adjusting for marital status, social class, smoking, alcohol use, and physical activity diminished these risks to 1.49 (95% CI: 1.16, 1.92), 1.35 (95% CI: 1.01, 1.82), and 1.93 (95% CI: 1.19, 3.12), respectively. Dissatisfaction was associated with increased disease mortality, particularly in men with heavy alcohol use (hazard ratio = 3.76, 95% CI: 1.61, 8.80). Women did not show similar associations between life satisfaction and mortality. Life dissatisfaction may predict mortality and serve as a general health risk indicator. This effect seems to be partially mediated through adverse health behavior. Am J Epidemiol 2000;152:983–91.