Data remain limited regarding the comparative long-term mortality across the spectrum of patients with different indications for percutaneous coronary intervention (PCI). We evaluated early and late mortality in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI compared with early and late mortality in patients undergoing PCI for unstable angina (UA) or non-STEMI (NSTEMI) and stable angina. A total of 10,549 consecutive patients undergoing PCI from 1997 to 2005 at a single institution were followed up prospectively (median 3.2 years, interquartile range 1.5 to 5.6) to assess all-cause mortality. The indication for PCI was STEMI in 28%, UA/NSTEMI in 32%, and stable angina in 40%. The mortality rate at 6 years was 18.9% in patients with STEMI, 16.2% in patients with UA/NSTEMI, and 11.7% in those with stable angina. During the initial 6 months, patients with STEMI had an increased risk of death compared with patients with UA/NSTEMI (relative risk [RR] 3.09, 95% confidence interval [CI] 2.46 to 3.89) and stable angina (RR 5.82, 95% CI 4.45 to 7.62). However, between 6 months and 6 years, mortality accrued at an almost similar rate among patients with STEMI and those with stable angina (RR 1.06, 95% CI 0.86 to 1.32) and mortality was greatest in patients with UA/NSTEMI (UA/NSTEMI vs stable angina: RR 1.33, 95% CI 1.11 to 1.58; STEMI vs UA/NSTEMI: RR 0.80, 95% CI 0.65 to 0.99). In conclusion, we have demonstrated that the inferior survival rates in patients with STEMI after primary PCI are mainly attributed to greater mortality in the first months after the event. These observations highlight that new adjunctive therapeutic strategies should aim at mortality reduction in the first months after primary PCI.