Previous observational studies have evaluated the utility of prolonged thienopyridine therapy in patients receiving drug-eluting stents, with conflicting results. A landmark analysis was therefore performed on the basis of the prospective, double-blind TAXUS-II SR, TAXUS-IV, and TAXUS-V trials. Of 2,736 randomized patients, 2,171 were event free at 1 year, of whom 964 (44.4%) at physician discretion were still taking thienopyridines at that time. Among the 1,141 event-free patients randomized to Taxus stents, a trend was present in those patients still taking compared with those having discontinued thienopyridines at 1 year to have numerically fewer very late stent thrombosis episodes at 2 years (0 vs 4 [0.7%] events, respectively, p = 0.07) and 5 years (4 [0.8%] vs 8 [1.4%] events, respectively, p = 0.43). However, in event-free Taxus patients taking compared with those not taking thienopyridines at 1 year, there were no significant differences in the 2- and 5-year rates of death (1.4% vs 0.6%, p = 0.22, and 6.0% vs 7.4%, p = 0.83, respectively) and death or myocardial infarction (1.8% vs 1.9%, p = 0.82, and 8.3% vs 9.8%, p = 0.75, respectively). There were no significant interactions between 1-year thienopyridine use status and stent type (Taxus vs bare-metal stent) on the individual or composite end points of stent thrombosis, death, or myocardial infarction at either 2 or 5 years (all interaction p values >0.50). In conclusion, thienopyridine use beyond 1 year after drug-eluting stent implantation may reduce stent thrombosis over the subsequent 12-month period, but the rates of death and myocardial infarction at 2 and 5 years are not prevented by extended thienopyridine use after either drug-eluting or bare-metal stent implantation.