This study sought to investigate whether there is a differential prognostic effect of successful percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) according to the target vessel the CTO is located in. Between 1998 and 2007, a total of 1,791 patients underwent PCI of a CTO at three tertiary care centers in the US, Italy, and South Korea. Patients with CTOs in multiple target vessels or the left main stem were excluded (n = 57). Of the remaining 1,734 patients, 609 had a CTO in the left anterior descending (LAD, 35.1%), 391 in the left circumflex (LCX, 22.5%), and 734 in the right coronary artery (RCA, 42.3%). Five-year mortality and the need for coronary artery bypass grafting (CABG) were compared between patients with successful vs. unsuccessful PCI stratified by target vessel. Procedural success was obtained in 71.1% of LAD patients, 69.1% of LCX patients, and 65.1% of RCA patients (P = 0.06). The mean follow-up duration was 1,178 days. Kaplan-Meier estimates of long-term mortality were 6.7% vs. 11.0% (P = 0.03), 5.5% vs. 13.9% (P < 0.01), and 6.6% vs. 4.1% (P = 0.80) in successful vs. unsuccessful LAD, LCX, and RCA patients, respectively. After multivariate analysis, successful CTO PCI remained associated with lower mortality in the LAD (HR 0.41, P = 0.02) and LCX groups (HR 0.32, P < 0.01). The need for CABG was lower after successful CTO PCI in all three groups (LAD 4.6% vs. 16.0%, P < 0.01; LCX 2.9% vs. 18.2%, P < 0.01, RCA 2.3% vs. 8.4%, P < 0.01). The results from this large contemporary cohort of patients suggest that successful PCI of a CTO in the LAD and the LCX, but not the RCA, is associated with improved long-term survival.