Diabetes mellitus (DM) increases the risk of adverse outcomes after coronary revascularization. Controversy persists regarding the optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD). Aim: The aim of this study was to assess the outcomes of drug-eluting stent (DES) insertion in DM and non-DM patients with complex coronary artery disease (CAD) after risk stratification by the percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score. Methods and results: We performed multivessel percutaneous coronary intervention (PCI) for 601 lesions in 243 DM patients and 1,029 lesions in 401 non-DM patients. All included patients had MVD and one or more lesions of type B2/C. The two-year outcomes and event rates were estimated in the DM and non-DM patients using Kaplan-Meier analyses. The baseline SYNTAX score was ≦22 in 84.8% vs. 84%, P = 0.804, and 23-32 in 15.2% vs. 16%, P = 0.804, of the DM and non-DM patients, respectively. The number of diseased segments treated (2.57 ± 0.75 vs. 2.47 ± 0.72; P = 0.066) and stents implanted per patient (2.41 ± 0.63 vs. 2.32 ± 0.54; P = 0.134) were similar in both groups. After a mean follow-up of 642 ± 175 days, there were no differences in the major adverse cardiac and cerebrovascular events (MACCE; 26.7% vs. 20.9%; P = 0.091), composite end point of all-cause death/ myocardial infarction (MI)/stroke (12.3% vs. 9%; P = 0.172), individual MACCE components of death (3.7% vs. 3.2%; P = 0.754), MI (6.6% vs. 4%; P = 0.142), and absence of stroke in the DM and non-DM patients. An increased need for repeat revascularization was observed in DM patients (18.5% vs. 10.2%; P = 0.003). In the multivariate analysis, DM was an independent predictor of repeat revascularization (hazard ratio: 1.818; 95% confidence interval: 1.162-2.843; P = 0.009). Conclusions: DES implantation provides favorable early and mid-term results in both DM and non-DM patients undergoing PCI for complex lesions. After a mean follow-up of two years, DM and non-DM patients with complex CAD treated by PCI using new-generation DES showed no differences with regard to MACCE and other secondary end points. However, higher rates of ischemia-driven repeat revascularization were observed in DM patients.