Combined antiplatelet therapy after coronary stent placement is superior to anticoagulation with respect to early outcome. It is unclear if this benefit is maintained during long-term follow-up. This study reports on the 4-year clinical outcome of patients randomized in the Intracoronary Stenting and Antithrombotic Regimen trial. In the Intracoronary Stenting and Antithrombotic Regimen trial, 517 patients were randomized after successful placement of Palmaz-Schatz stents: 257 to aspirin and ticlopidine, and 260 to aspirin and phenprocoumon. Ticlopidine and phenprocoumon were given for 4 weeks. At 30 days, patients with ticlopidine had significantly fewer adverse cardiac events (1.6% vs 6.2%; p = 0.007), nonfatal myocardial infarction (0.8% vs 3.5%; p = 0.034), and target vessel revascularization procedures (1.2% vs 5.4%; p = 0.007). At 4 years, rates for any adverse cardiac events were 22.6% versus 28.5% (p = 0.078), for nonfatal myocardial infarction 0.9% versus 5.8% (p = 0.003), and for target vessel revascularization 18.3% versus 22.7% (p = 0.21). The absolute difference in event rates (4.6% after 30 days) was maintained after 4 years (5.9%). Event rates beyond day 30 were not significantly different (21.1% vs 22.5%; p = 0.78), nor were the rates beyond the first year, which were very low (5.2% vs 3.6%; p = 0.50). This study shows that the benefit of combined antiplatelet therapy evident after 30 days is maintained after 4 years. Independent of the initial regimen, rates of adverse cardiac events are low beyond the first year.