Objectives The aim of this study was to compare the efficacy and safety of drug-eluting stent (DES) and bare-metal stent (BMS) use in chronic total occlusion (CTO) recanalization. Background The long-term effectiveness and safety of DES use in CTO recanalization are unclear, and performance of randomized clinical trials in the field is complex. Methods Major electronic information sources were explored for articles comparing outcomes with DES and BMS use among patients with CTO. Assessed clinical outcomes were death, myocardial infarction, target vessel revascularization, major adverse cardiac events, and stent thrombosis; angiographic outcomes were stent restenosis and stent reocclusion. Results Fourteen comparative studies were identified (a total of 4,394 patients). When compared with BMS, DES significantly reduced risk of major adverse cardiac events (relative risk [RR]: 0.45, 95% confidence interval [CI]: 0.34 to 0.60, p < 0.001) and TVR (RR: 0.40, 95% CI: 0.28 to 0.58, p < 0.001) without increasing death (RR: 0.87, 95% CI: 0.66 to 1.16, p = 0.88) or myocardial infarction (RR: 0.89, 95% CI: 0.54 to 1.46, p = 0.80). This benefit was sustained at >= 3 years of follow-up. Lower RRs for restenosis (RR: 0.25, 95% CI: 0.16 to 0.41, p < 0.001) and stent reocclusion (RR: 0.30, 95% CI: 0.18 to 0.49, p < 0.001) were also observed in the DES group. A strong trend toward a higher rate of stent thrombosis was documented in DES-treated patients (RR: 2.79, 95% CI: 0.98 to 7.97, p = 0.06). Conclusions DES use in CTO recanalization is associated with significantly fewer major adverse cardiac events and fewer occurrences of target vessel revascularization, restenosis, and stent reocclusion than with BMS. Although a statistical trend toward a higher risk of stent thrombosis was observed, the use of DES in this context seems to be safe, with an overall benefit sustained in the long term. (J Am Coll Cardiol 2010; 55: 1854-66) (C) 2010 by the American College of Cardiology Foundation