Despite high levels of cardiovascular risk factors, Mexican Americans paradoxically have a lower prevalence of cardiovascular disease. A possible explanation is that conventional cardiovascular risk factors have a lesser impact on this ethnic group. In the present study, a 7- to 8-year follow-up of the San Antonio Heart Study cohort was used to estimate total and cardiovascular disease mortality and their association with baseline risk factors. A total of 2,629 Mexican Americans form the basis of this study, and 1,136 non-Hispanic whites from the same cohort served as the comparison group. The age- and sex-adjusted rates for total death and cardiovascular disease death were somewhat higher in Mexican Americans than non-Hispanic whites (rate ratio for total mortality = 1.4,95% confidence interval 1.0–2.0; and rate ratio for cardiovascular mortality = 1.3,95% confidence interval 0.7–2.4). After adjustment for sex, age, and socioeconomic status in multivariate analyses, current smoking, diabetes, high cholesterol, and hypertension were positively associated with all-cause mortality and cardiovascular disease mortality in Mexican Americans. Overall, these risk factors accounted for 45% of all-cause mortality and 55% of cardiovascular disease mortality in this ethnic group. In comparison, the risk factors accounted for 46% of all-cause mortality and 46% of cardiovascular disease mortality in non-Hispanic whites. The authors conclude that cigarette smoking, diabetes, high cholesterol, and hypertension are important predictors of both all-cause and cardiovascular disease deaths in Mexican Americans. There was no evidence for a diminished effect of these risk factors in Mexican Americans. Am J Epidemiol 1996;144:1058-65.