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Data on the efficacy and safety of drug-eluting stent (DES) for treatment of multiple coronary chronic total occlusion (CTO) lesions are scanty. The aim of the present study was to compare the long-term outcomes of DES versus bare metal stent (BMS) implantation for multiple coronary CTO lesions.We analyzed 188 patients who underwent coronary stenting for at least two de novo CTO lesions in our center from November 2000 to November 2006. Among them, 118 patients (62.8%) received DES and 70 patients (37.2%) received BMS implantation after the recanalization for CTO lesions. All patients were followed up for up to 5 years for the occurrence of major adverse cardiac events (MACE). Long-term survival rates were estimated with the Kaplan-Meier method.There were no significant differences in baseline clinical characteristics and procedural success rate between DES group and BMS group. Compared with the BMS group, the DES group showed a significantly higher rate of long CTO (> 15 mm) (62.0% vs. 50.6%, P=0.023). The number of stents per lesion (1.39±0.71 vs. 1.17±0.66, P=0.007) and the mean length of stents in the DES group were also higher than those in the BMS group ((40.8±11.4) mm vs. (23.4±8.7) mm, P<0.001). But the mean diameter of stents in the DES group was smaller than that in the BMS group ((3.1±0.2) mm vs. (3.3±0.5) mm, P <0.001). Average follow-up time was 4.8±0.7 (1.5–5.0) years in the BMS group and 4.3±0.5 (1.3–5.0) years in the DES group. Both the 5-year cumulative survival rates and the target vessel revascularization (TVR)-free survival rates of the DES group were significantly higher than those in the BMS group (83.1% vs. 72.9%, Log-rank P=0.044; 77.1% vs. 62.9%, Log-rank P=0.009). The cumulative MACE-free survival rates in the DES group were significantly higher than those in the BMS group (71.2% vs. 51.4%, Log-rank P=0.001). Multivariable Cox regression analysis demonstrated that DES implantation for multiple CTO lesions could significantly reduce the long-term MACE risk after percutaneous coronary intervention (PCI) (HR: 0.436; 95%CI 0.327–0.665, P <0.001). Age over 65 years (HR: 2.018; 95%CI 1.491–3.127, P <0.001) and left ventricular ejection fraction <50% (HR: 1.494; 95%CI 1.125–2.376, P <0.001) were identified as the independent predictors of long-term MACE.This study demonstrates the long-term (up to 5 years) efficacy and safety of DES for treatment of multiple coronary CTO lesions, and its superiority compared to BMS in reducing the rates of TVR and MACE.