Background The long-term safety of drug-eluting stents (DES) for the treatment of ST-segment elevation myocardial infarction (STEMI) is unclear and may differ from that in stable angina (stable) patients as noted in autopsy studies. Methods To assess this problem, 210 consecutive STEMI and 323 stable patients, randomized 2:1 to DES versus bare-metal stents (BMS), were followed up for 3 years for definite/probable stent thrombosis (ST) and cardiac death/myocardial infarction. Events occurring during the initial 6 months were separated from later events. Results The 3-year rate of ST was 8.1% in STEMI vs 3.4% in stable patients ( P = .02), with corresponding rates of 9.4% vs 2.9% ( P = .01) for DES and of 5.6% vs 4.3% ( P = .71) for BMS patients, respectively. This difference appeared only after 6 months: 4.6% in STEMI vs 1.7% in stable patients ( P = .05) and in DES-treated patients (6.2% vs 2.0%, P = .05). Results of ST were paralleled by findings of clinical events, although here differences were less pronounced, but also seen only late after stenting. Thus, in STEMI patients, late events occurred more frequently after DES vs BMS implantation (11.6% vs 3.0%, P = .04), compared to results in stable patients (DES 6.4%, BMS 1.9%, P = .08). Conclusions In this pilot study, we observed an increased rate of late ST and a trend to more related clinical events in patients after stenting for STEMI vs for stable angina, particularly if treated with DES. This may explain outcome differences between results of pivotal trials in stable patients vs those of “real-world” patients.