OBJECTIVE: Several studies have examined the influence of smoking cessation on weight gain. However, to date no study has examined this association in Mexican Americans (MA). DESIGN: Using data collected from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease, we examined the association between smoking cessation and weight gain in 1930 Mexican Americans and 1126 non-Hispanic whites (NHW). Smoking cessation was defined as self-reported smoking at baseline but not at follow-up. RESULTS: Although there was no significant ethnic difference in the prevalence of smoking at baseline (27.2% in MA and 25.4% in NHW, P = 0.309), a greater proportion of MA smoked at follow-up compared to NHW (19.7% vs 16.5%, P = 0.037). However, there was no significant ethnic difference in the percentage of individuals who stopped smoking during the follow-up period. A two-fold greater percentage of MA quitters than NHW quitters became overweight or obese, defined as a body mass index greater than or equal to 25 kg/m2 (7.4% vs 3.1%). However, this difference did not quite reach statistical significance (P = 0.072). Using linear regression to predict change in weight or body mass index from baseline to follow-up, smoking cessation was predictive of either weight gain or BMI gain in both ethnic groups. However, smoking status accounted for only 1.0% of the variance in these outcomes, and the estimated risk of becoming overweight or obese attributable to smoking cessation was only 7.4% in MA and 3.1% in NHW. CONCLUSION: We conclude that there is an ethnic difference in the influence of smoking cessation on weight gain in MA and NHW. However, in both ethnic groups this effect is quite small and makes only a slight contribution to the overall increase in prevalence of obesity in this population.