BACKGROUND: We aimed to appraise the outcomes of diabetic patients with unprotected left main (ULM) disease treated with drug-eluting stents. Percutaneous coronary intervention with drug-eluting stent implantation is increasingly used for ULM disease. However, there are no data on the clinical results of drug-eluting stents for ULM disease in patients with diabetes. METHODS: We collected baseline and outcome data from all patients undergoing percutaneous coronary intervention with drug-eluting stents for ULM disease at our institution since 2002. We identified three groups: insulin-requiring diabetes mellitus patients, noninsulin-requiring diabetes mellitus patients, and nondiabetes mellitus individuals. The primary end point was the rate of major adverse cardiac events, that is, cardiac death, myocardial infarction, or target vessel revascularization. We also appraised stent thrombosis according to the Academic Research Consortium. RESULTS: A total of 185 patients were enrolled, 25/185 (14%) insulin-requiring diabetes mellitus patients, 30/185 (16%) noninsulin-requiring diabetes mellitus patients, and 130/185 (70%) nondiabetes mellitus individuals. In-hospital adverse events were overall uncommon and not significantly different across groups. After a median follow-up period of 23.1 months, major adverse cardiac events had occurred in similar rates across groups: 6/25 (24%) insulin-requiring patients with diabetes mellitus, 8/30 (27%) noninsulin-requiring patients with diabetes mellitus, and 31/128 (24%) nondiabetes mellitus individuals (P = 0.96). No case of definite or probable stent thrombosis was adjudicated. Intriguingly, possible stent thrombosis was nonsignificantly more common among insulin-requiring diabetes mellitus patients than among noninsulin-requiring diabetes mellitus patients or nondiabetes mellitus individuals [1/25 (4%) vs. 0/30 (0%) and 1/128 (0.8%), respectively, P = 0.30]. CONCLUSION: Drug-eluting stents provide favorable early and long-term results in both selected patients with diabetes and nondiabetic individuals undergoing percutaneous coronary intervention for ULM disease. Nonetheless, further randomized data are eagerly awaited to definitely confirm or disprove these findings.