We tested the hypothesis that in patients with acute myocardial infarction (AMI), concomitant diabetes mellitus (DM) and renal failure (RF) increases the short- and long-term risk compared to DM or RF alone.This registry included consecutive patients with AMI treated with percutaneous coronary intervention (PCI) who completed 1-year follow-up. The primary outcome included the rate of all causes of death, AMI, and target vessel revascularization (TVR).A total of 858 patients were studied in 4 groups: DM and RF, 112 (13.1%); DM alone, 145 (16.9%); RF alone, 134 (15.6%); and no DM or RF, 467 (54.4%). The DM and RF group had more cardiogenic shock, lower ejection fraction, longer hospital stay, and higher peak troponin (all p<0.01). After multivariable adjusted analysis, the DM and RF group had higher risk of death (HR 3.35, CI 1.69–6.67; p<0.01), AMI (HR 2.8; CI 1.15–6.83; p=0.02), and major adverse cardiac events (HR 1.97, CI 1.23–3.13; p<0.01) at 1-year follow-up compared to patients with no DM or RF.The combination of DM and RF is the strongest independent predictor of death and AMI, but not a predictor of TVR. These findings should be evaluated in large prospective studies.