Objective:The metabolically healthy (MHO) and unhealthy obese (MUHO) differ in terms of cardiovascular risk. However, little is known about predicting the development of these phenotypes and the future stability of the MHO phenotype. Therefore, we examined these two issues in the San Antonio Heart Study.Design:Longitudinal, population-based study of cardiometabolic risk factors among Mexican Americans and non-Hispanic whites in San Antonio.Subjects:The study sample included 2368 participants with neither MUHO nor diabetes at baseline. Median follow-up was 7.8 years. MHO was defined as obesity with ⩽1 metabolic abnormality; MUHO, as obesity with ⩾2 abnormalities.Results:At baseline, 1,595 and 498 individuals were non-obese with ⩽1 and ⩾2 metabolic abnormalities, respectively; 275 were MHO. Among non-obese individuals, independent predictors of incident MHO (OR for 1-SD change [95% CI]) included body mass index (8.12 [5.66-11.7]), triglycerides (0.52 [0.39-0.68]), and HDL-C (1.41 [1.11-1.81]), whereas independent predictors of incident MUHO included BMI (5.97 [4.58-7.77]) and triglycerides (1.26 [1.05-1.51]). Among participants with ⩽1 metabolic abnormality, obesity was associated with greater odds of developing multiple metabolic abnormalities (OR 2.26 [1.74-2.95]).Conclusions:Triglycerides and HDL-C may be useful for predicting progression to MHO. MHO may not be a stable condition, because it confers an increased risk of developing multiple metabolic abnormalities.International Journal of Obesity accepted article preview online, 02 July 2014; doi:10.1038/ijo.2014.113.