Objective This study was carried out to determine the effect of the use of dual antiplatelet therapy (DAPT) for more than 12 months on long-term clinical outcomes in patients who had undergone a percutaneous coronary intervention with the first and second generations of drug-eluting stents (DES). Background The potential benefits of the use of DAPT beyond a 12-month period in patients receiving DES have not been established clearly. Moreover, it is also unclear whether the optimal duration of DAPT is similar for all DES types. Methods A total of 2141 patients with coronary artery disease treated exclusively with Cypher sirolimus-eluting stents (SES) or Endeavor zotarolimus-eluting stents (ZES) were considered for retrospective analysis. The primary endpoint [a composite of all-cause mortality, nonfatal myocardial infarction (MI), and stroke] was compared between the 12-month DAPT and the >12-month DAPT group. Results A total of 1870 event-free patients on DAPT at 12 months were identified. The average follow-up was 28.2 +/- 7.4 months. The primary outcomes were similar between the two groups (4.1% 12-month DAPT vs. 1.9% >12-month DAPT; P = 0.090). Incidences of death, MI, stroke, and target vessel revascularization did not differ significantly between the two groups. Subgroup analysis showed that in the patients with hypertension, >12-month DAPT significantly reduced the occurrence of death/MI/stroke compared with that in the 12-month DAPT group (P = 0.04). In patients implanted with SES, the primary outcome was significantly lower with the >12-month DAPT group (5.2% 12-month DAPT vs. 1.6% >12-month DAPT; P = 0.016), whereas in patients with ZES, the primary outcome was comparable between the two groups (2.3% 12-month DAPT vs. 2.0% >12-month DAPT; P = 0.99). Conclusion In our study, for all patients, >12-month DAPT in patients who had received DES was not significantly more effective than 12-month DAPT in reducing the rate of death/MI/stroke. Our findings, that patients who received SES benefit from >12-month DAPT whereas extended use of DAPT was not significantly more effective in those implanted with ZES, implied that the optimal duration of DAPT was different depending on different types of DES. Coron Artery Dis 24:217-223 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Coronary Artery Disease 2013, 24:217-223