Background The occurrence of in-stent restenosis(ISR)coronary chronic total occlusion(CTO)is presently increasing. However,there were few data related to the long-term clinical outcomes after percutaneous coronary intervention(PCI)between ISR CTO and de novo CTO. Methods A total of 435 CTO patients who had at-tempted PCI between Jan 2013 and November 2017 were screened for inclusion in this study. The Kaplan-Meier method was applied to estimate event-free survival and the log-rank test to compare long-term outcome. Cox re-gression analysis was used to identify associations between adverse events and risk factors. Results There were 84 ISR CTO cases and 351 de novo CTO cases in this study. Successful revascularization was achieved similar between ISR CTO group and de novo CTO group (84.5％ vs. 87.2％,P=0.592). The prevalence of MACE [17.9％ vs. 9.1％;hazard ratio(HR):2.323;95％ confidence interval(CI)1.233-4.37;P=0.004]and TLR (8.3％vs. 3.4％;HR:2.627;95％CI 1.05-6.53;P<0.016)were higher in the ISR CTO group,during the 2-year follow-up. Conclusions The procedural success rate of ISR CTO achieved was comparable to that of de novo CTO in the contemporary practice. But the long-term clinical outcome was significantly worse in term of major adverse cardiac events and target lesion revascularization.