Objectives: To describe clinical outcome after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) due to graft failure. Background: Limited data are available on outcome after PCI for graft failure‐induced ACS in the drug‐eluting stent (DES) era. Methods: Patients were identified who underwent PCI either with DES or BMS for ACS due to graft failure between January 2003 and December 2008. Follow‐up was performed at 1 year and April 2011. The primary endpoint was the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR). Kaplan–Meier estimates were calculated at 1 and 5‐year follow‐up. Predictors were identified by backward selection in Cox proportional hazards models. Results: A total of 92 patients underwent PCI, of which 77 were treated with bare metal stents (BMS) and 15 with DES. Patient and procedural characteristics were similar in both groups. Mean follow‐up was 3.2 years. Five‐year composite event rate was 65.9% after BMS vs. 43.4% after DES implantation (P = 0.17). Individual endpoints were comparable in both groups. Recurrence of angina, hospitalization, and repeat interventions were similar. After multivariable adjustment, the use of DES was not associated with a significant reduction in the primary endpoint (HR = 0.44, 0.18–1.04, p = 0.06). Conclusion: In patients presenting with ACS due to acute graft failure, long‐term outcomes remain poor. In a nonrandomized comparison with BMS, DES use was not associated with significant improved long‐term clinical outcomes. © 2012 Wiley Periodicals, Inc.