Patients with previous percutaneous coronary intervention (PCI) are often excluded from clinical trials. As a result, limited data are available on the long-term outcome of such patients undergoing repeat PCI. In this study, we assessed the impact of previous PCI on outcomes in patients undergoing repeat PCI. We compared the baseline features and outcomes of 7,056 patients without previous PCI (group I) with those of 1,281 patients with previous PCI of the original target lesion (group II) and 1,408 patients with previous PCI of a nontarget lesion (group III) undergoing PCI in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) trial. Compared with patients in group I, patients in groups II and III were more likely to have diabetes (25% and 24% vs 21%, p <0.02), previous myocardial infarction (51% and 56% vs 29%, p <0.001), and ostial lesions (10% and 7% vs 5%, p <0.001), and less likely to have, as their indication for PCI, myocardial infarction (2% and 7% vs 17%, p <0.001). At 1 month, major adverse cardiac events, including death, myocardial infarction, and repeat revascularization, were low and similar in all 3 groups. Compared with patients in group I, the risk of major adverse cardiac events at 9 months was significantly increased for patients in groups II (34.1% vs 18.6%, relative risk [RR] 2.03, adjusted RR 1.78, 95% confidence interval 1.58 to 2.01) and III (23.9% vs 18.6%, RR 1.30, adjusted RR 1.16, 95% confidence interval 1.02 to 1.33). The increased risk of major adverse cardiac events was entirely due to higher rates of repeat revascularization. In conclusion, despite similar short-term outcomes, patients with previous PCI undergoing PCI of either target or nontarget lesions had lower event-free survival at 9 months of follow-up.