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Background The Orsiro is a hybrid stent which has passive (amorphous silicon carbide) and active (poly-L-lactic acid, PLLA) coatings. The first layer encapsulates the stent struts, promoting lower local inflammation, whereas the second layer releases sirolimus through a biodegradable matrix. This study's aim was to compare the results of percutaneous coronary interventions (PCI) with Orsiro and Xience™ V stents (everolimus-eluting stent) in daily clinical practice. Methods Observational study in which patients were divided into two groups: those who received only one or more Orsiro stents, and those who received only XienceTM V stents. Early and late outcomes were prospectively collected. Results Between September 2012 and March 2014, this study included 92 and 108 patients treated with Orsiro and Xience™ V stents, respectively. Clinical, angiographic, and procedure characteristics were mostly similar between groups. Rates of procedure success (98.9% vs. 95.4%; p = 0.22), in-hospital mortality (1.1% vs. 0%; p = 0.40) and stent thrombosis (0% vs. 0.9%, p = 0.30) did not differ between groups. Time of follow-up was 434 ± 111 and 477 ± 66 days (p = 0.23), respectively, and differences in mortality (0.9% vs. 0%, p = 0.30), stent thrombosis (0% vs. 0.9%; p = 0.30), or need for repeat revascularization of the target lesion (0% vs. 0.9%; p = 0.30) were not observed. Conclusions Orsiro and Xience™ V stents showed similar performance, with low rates of early and late clinical and angiographic events.