Recent meta-analyses suggest an increased risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM) treated with rosiglitazone. These meta-analyses have drawn considerable criticisms. Retrospective observational studies do not consistently support this association. The objective of this study was to compare rates of adverse cardiovascular outcomes in T2DM patients treated with rosiglitazone alone or combined with metformin or metformin alone. This retrospective study, using the health maintenance organization database, included patients who were dispensed rosiglitazone (alone or with metformin) for at least 6 months as follows: rosiglitazone alone (n = 745), rosiglitazone and metformin (n = 2753), and metformin alone (n = 11 938). Adverse cardiovascular outcomes were new diagnosis of AMI, acute coronary syndrome (ACS), coronary revascularization (CRV), congestive heart failure (CHF), and all-cause mortality. Mean on-treatment follow-up was 30 months. After adjustment for covariates found to be significant in univariate analyses, rosiglitazone was associated only with CHF (hazard ratio [HR] = 2.23; 95% confidence interval [CI]: 1.41-1.95) with no increase of risk for AMI (HR = 1.13; 95%CI: 0.60-2.12), ACS (HR = 0.85; 95% CI: 0.57-1.26), coronary revascularization (HR = 1.22; 95% CI:0.82-1.54), or all-cause mortality (HR = 1.15; 95% CI: 0.85-1.56). In this community-based cohort, 30 months of therapy with rosiglitazone treatment was associated with increased risk of CHF but was not associated with increased risk of AMI, ACS, coronary revascularization, or all-cause mortality.