Objectives The aim of this study was to evaluate long-term clinical outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). Background Despite technical advancements, there is a paucity of data on long-term outcomes after PCI of CTO. Methods We evaluated long-term clinical outcomes in 1,791 patients who underwent PCI of 1,852 CTO at 3 tertiary care centers in the United States, South Korea, and Italy between 1998 and 2007. Median follow-up was 2.9 years (interquartile range: 1.5 to 4.6 years). Results Procedural success was obtained in 1,226 (68%) patients. Stents were implanted in 1,160 patients (95%); 396 patients (34%) received bare-metal stents (BMS), and 764 patients (66%) received drug-eluting stents (DES). After multivariable analysis, successful CTO PCI was an independent predictor of a lower cardiac mortality (hazard ratio HR: 0.40, 95% confidence interval CI: 0.21 to 0.75, p < 0.01) and reduced need for coronary artery bypass graft surgery (HR: 0.21, 95% CI: 0.13 to 0.40, p < 0.01); it also correlated with a strong trend toward lower all-cause mortality (HR: 0.63, 95% CI: 0.40 to 1.00, p = 0.05) at 5-year follow-up. Among patients who underwent stent implantation, treatment with DES rather than BMS resulted in less target vessel revascularization at long-term follow-up (17.2% vs. 31.1%, p < 0.01); definite/probable stent thrombosis rates were similar (DES 1.7%, BMS 2.3%, p = 0.58). Within the DES subgroup, patients treated with paclitaxel-eluting stents and sirolimus-eluting stents had similar clinical outcomes. Conclusions Successful CTO PCI is associated with reduced long-term cardiac mortality and need for coronary artery bypass graft surgery. Treatment of CTO with DES rather than BMS is associated with a significant reduction in target vessel revascularization with similar rates of stent thrombosis. Paclitaxel-eluting stents and sirolimus-eluting stents had similar long-term safety and efficacy outcomes.