Studies on chronic total occlusion (CTO) treatment strategy in stable patients have reported conflicting results. We focused on stable diabetic patients with a single CTO (other vessels have been successfully treated before). We attempted to identify which strategy (percutaneous coronary intervention [PCI] or medical therapy [MT]) is optimal; 545 patients were selected from a total of 39 952 patients. Based on the initial treatment strategy, we assigned patients to either the PCI or MT group. The primary end point was a major adverse cardiac event (MACE). After a median follow-up of 45 months (interquartile range: 25.7-79.2 months), we observed (1) no difference in MACE and myocardial infarction between groups, (2) multivariate analysis showed that PCI group was superior to MT group in cardiac death (hazard ratio: 4.758 (1.698-13.334); P = .003) and all-cause death (2.767 [1.157-6.618]; P = .022). The superiority was consistent in propensity score-matched analysis, and (3) a failed PCI group was not associated with higher risks in the clinical end points, except for target vessel revascularization, compared with MT. We concluded that for stable patients with diabetes and one single CTO, initial PCI strategy tended to offer patients survival benefits compared with MT.