BACKGROUND Patients with diabetes mellitus have a higher risk of cardiovascular events and death than those without diabetes. METHODS The ���all-comers��� design, ZEST trial was designed to compare the second-generation zotarolimus-eluting stent with the first-generation sirolimus-and paclitaxel-eluting stent for percutaneous coronary revascularization (PCI) in daily practice, and 2645 patients were enrolled. Randomization was stratified by the status of diabetes. The primary outcome was a composite of major adverse cardiac events (death, myocardial infarction [MI], and ischemia-driven target-vessel revascularization [TVR]). RESULTS A total of 760 diabetic patients (1080 lesions) received a zotarolimus (268 patients, 365 lesions), sirolimus (247 patients, 360 lesions), or paclitaxel (245 patients, 355 lesions)-eluting stent. Baseline clinical and angiographic characteristics were similar in the three groups. At 24 months, the zotarolimus-stent group showed similar rates of major adverse cardiac events compared with the paclitaxel-stent group (13.8% vs. 15.3%, P=0.58), but trend toward higher rates of events compared with the sirolimus-stent group (13.8% vs. 7.7%, P=0.052). The incidence of death or MI was similar among the groups (zotarolimus- vs. sirolimus- vs. paclitaxel-stent, 8.2% vs. 6.9% vs. 9.6%, respectively, P=0.57), but the rate of TVR significantly differ (zotarolimus- vs. sirolimus- vs. paclitaxel-stent, 7.2% vs. 1.7% vs. 7.4%, respectively, P=0.02). A nonsignificant trend was detected in favor of the sirolimus-stent group in the rate of definite or probable stent thrombosis (zotarolimus- vs. sirolimus- vs. paclitaxel-stent, 1.5% vs. 0% vs. 1.9%, respectively, P=0.14). CONCLUSIONS In diabetic patients who underwent PCI, the use of zotarolimus-eluting stents results in similar rates of major adverse cardiac events compared with paclitaxel-eluting stents, and in higher rates of major adverse cardiac events compared with sirolimus-eluting stents at 2-year follow-up.