OBJECTIVES: This study sought to evaluate the long-term safety of the zotarolimus-eluting stent (ZES) using a pooled analysis of pivotal trials. BACKGROUND: Drug-eluting stents, compared with bare-metal stents (BMS), have reduced restenosis; however, individual trials of these stents have not had sufficient power to ascertain long-term safety. METHODS: We combined patient level data from 6 prospective randomized single-arm multicenter trials involving 2,132 patients treated with ZES and 596 patients treated with a BMS control. The median follow-up was 4.1 years, with 5-year follow-up completed in 1,256 patients (97 of those eligible). The recommended minimum duration of dual antiplatelet therapy in these studies was 3 to 6 months regardless of stent type. An independent events committee adjudicated all events. The 2 treatment groups were compared after adjustment for between trial variation and for individual patient clinical and angiographic characteristics by propensity score.