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Objective: The goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes., Research Design and Methods: Five specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1 ) a subcohort of the Veterans Affairs Diabetes Trial (VADT) ( n = 445) and 2 ) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study ( n = 271)., Results: Increased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A 1c . In the VADT, increased risk of incident CVD events ( n = 107) was associated with lower MetSO after adjusting for age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28-0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events ( n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18% and 15%, respectively; P = 0.04 for both); however, only the difference in MetSO remained significant after adjustment for prior CVD event ( P = 0.002)., Conclusions: Lower levels of MetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes., (© 2017 by the American Diabetes Association.)