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Drug-eluting stents (DESs) are commonly used in patients with unprotected left main (ULM) disease. Although multivessel disease and stenting are frequent in this population, pertinent details on short-term and long-term outcomes are lacking.We identified consecutive patients with DES treatment for ULM. We distinguished patients presenting isolated ULM stenting (group A) from those with additional treatment of at least another major vessel (group B). The primary end point was major adverse cardiovascular events (i.e. death, myocardial infarction or target vessel revascularization). We compared the impact of a DES-only versus a hybrid DES and bare metal stent strategy for non-ULM lesions.A total of 189 patients were included, 25% in group A and 75% in group B. In-hospital events were similarly favorable (cardiac death in 0 and 2%, respectively, P = 0.58). A total of 99% patients were followed for a median of 25 months, yielding major adverse cardiovascular events in 17 and 37.5% (P = 0.011). Specifically, death occurred in 4 and 8.5% (P = 0.52), cardiac death in 0 and 7% (P = 0.12), myocardial infarction in 6.5 and 9% (P = 0.76) and target vessel revascularization in 4.3 and 22% (P = 0.006). Adoption of a systematic DES-only strategy for non-ULM lesions conferred significant benefits on major adverse cardiovascular events and repeat non-ULM revascularizations in comparison to a hybrid strategy (22 versus 45%, P < 0.001, and 9 versus 19%, P = 0.004, respectively), at both bivariate and multivariable analyses.Multivessel stenting on top of DES implantation for ULM can be performed with favorable early results. Systematic DES implantation for both ULM and non-ULM lesions is pivotal to maximize clinical results and minimize long-term recurrences.