This study examines the cardiovascular disease (CVD) risk profiles of first generation (FG) and second generation (SG) Mexican-Americans (MA) in two large national studies--the Hispanic Health and Nutrition Examination Study (HHANES) (1982-1984) and the National Health and Examination Study (NHANES) (1999-2004). The main outcome measures were five individual risk indicators of CVD (total cholesterol, HDL cholesterol, hypertension, diabetes, and smoking) and a composite measure (the Framingham Risk Score [FRS]). The analyses included cross-survey (pseudocohort) and within-survey (cross-sectional) comparisons. In multivariate analyses, SG men had higher rates of hypertension and lower rates of smoking than FG men; and SG women had lower total cholesterol levels, higher rates of hypertension, and lower rates of smoking than FG women. There was no generational difference in the FRS in men or women. The cross-survey comparisons detected generational differences in CVD risk factors not detected in within-survey comparisons, particularly among MA women. Future studies of generational differences in risk should consider using pseudocohort comparisons when possible.