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Background: Diabetes mellitus (DM) is highly prevalent among patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Therefore, the purpose of our study was to investigate the clinical outcomes of CTO-PCI in patients with or without DM. Methods: All relevant articles published in electronic databases (PubMed, Embase, and the Cochrane Library) from inception to August 7, 2020 were identified with a comprehensive literature search. Additionally, we defined major adverse cardiac events (MACEs) as the primary endpoint and used risk ratios (RRs) with 95% confidence intervals (CIs) to express the pooled effects in this meta-analysis. Results: Eleven studies consisting of 4238 DM patients and 5609 non-DM patients were included in our meta-analysis. For DM patients, successful CTO-PCI was associated with a significantly lower risk of MACEs (RR = 0.67, 95% CI 0.55–0.82, p = 0.0001), all-cause death (RR = 0.46, 95% CI 0.38–0.56, p < 0.00001), and cardiac death (RR = 0.35, 95% CI 0.26–0.48, p < 0.00001) than CTO-medical treatment (MT) alone; however, this does not apply to non-DM patients. Subsequently, the subgroup analysis also obtained consistent conclusions. In addition, our study also revealed that non-DM patients may suffer less risk from MACEs (RR = 1.26, 95% CI 1.02–1.56, p = 0.03) than DM patients after successful CTO-PCI, especially in the subgroup with a follow-up period of less than 3 years (RR = 1.43, 95% CI 1.22–1.67, p < 0.0001). Conclusions: Compared with CTO-MT alone, successful CTO-PCI was found to be related to a better long-term prognosis in DM patients but not in non-DM patients. However, compared with non-DM patients, the risk of MACEs may be higher in DM patients after successful CTO-PCI in the drug-eluting stent era, especially during a follow-up period shorter than 3 years. [ABSTRACT FROM AUTHOR]