Introduction: Cigarette flavorings, with the exception of menthol, have been banned under the Family Smoking Prevention and Tobacco Control Act. The U.S. Food and Drug Administration has the authority to regulate tobacco product constituents, including the use of menthol, if the scientific evidence indicates harm; however few studies have evaluated the health effects of menthol as compared to nonmenthol cigarette use. Objective: To investigate the prospective associations of cigarette smoking and menthol cigarette use with all cause, cancer and cardiovascular mortality in U.S. adults. Methods: We studied 10,158 adults 20 years of age and older who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999-2004 and were followed for an average of 4.7 years. Results: Fifty-five percent of participants were never smokers compared to 23%, 17% and 5% of former, current nonmenthol and current menthol cigarette smokers, respectively. The multivariable adjusted hazard ratios (95% confidence intervals [CI]) for former, current nonmenthol cigarette smokers and current menthol cigarette smokers compared to never smokers were 1.21 (0.93, 1.56), 2.46 (1.57, 3.83) and 2.10 (1.21, 3.66), respectively, for all-cause mortality, 0.86 (0.58, 1.27), 2.10 (1.05, 4.21) and 3.53 (1.55, 8.02) for cardiovascular mortality, 1.32 (0.73, 2.38), 4.04 (1.96, 8.35) and 5.50 (1.90, 15.88) for heart disease mortality and 1.94 (1.23, 3.05), 3.88 (2.21, 6.80) and 2.08 (1.01, 4.28) for cancer mortality. Compared to current nonmenthol cigarette smokers, adjusted hazard ratios (95% CI) for current menthol cigarette smokers were 0.87 (0.54, 1.42) for all-cause mortality, 1.66 (0.75, 3.68) for cardiovascular mortality, 1.39 (0.52, 3.67) for heart disease mortality and 0.57 (0.28, 1.18) for cancer mortality. Conclusions: In a representative sample of U.S. adults, menthol cigarette smoking was associated with increased all-cause, cardiovascular and cancer mortality with no differences compared to nonmenthol cigarettes, except maybe an increased risk for cardiovascular disease.