Background: Many studies have reported potential benefits of percutaneous coronary intervention (PCI) versus optimal drug therapy (ODT) for patients with stable coronary heart disease but with inconsistent results. To examine this, an explicit systematic review and meta-analysis was conducted to compared the clinical outcomes of PCI and ODT in these patients. Methods: The following terms were combined to search relative articles through databases PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science published from January 2010 to November 2021 according to Participants, Intervention, Control, Outcomes, Study (PICOS) criteria:"coronary heart disease", "stable coronary heart disease", "stable angina pectoris", "percutaneous coronary intervention", "PCI", "percutaneous transluminal coronary angioplasty", "drug therapy", "optimized drug treatment", and "optimized drug therapy". The meta-analysis was performed by RevMan 5.2, and the Cochrane risk of bias tool was used to evaluate the quality of the included studies.Results: A total of 12 articles were included in the final analysis. There were 4,288 cases of PCI patients and 4,261 cases of ODT patients. The results showed that, when comparing PCI with ODT, there was a significant difference in the probability of myocardial infarction [relative risk (RR) =0.63; 95% confidence intervals (CI): 0.45-0.90] and the patient mortality (RR =0.51; 95% CI: 0.40-0.64). However, there was no significant difference in the prevalence of stroke (RR =1.33; 95% CI: 0.82-2.17), revascularization (RR =0.86; 95% CI: 0.46-1.62) and patient quality of life (MD =10.44; 95% CI: −1.84 to 22.73). Performance bias and detection bias were all unclear in the included studies and should be warned.Discussion: Compared with ODT, PCI reduced the mortality and myocardial infarction rate of patients with CTO or severe coronary artery stenosis. However, the incidence of stroke, revascularization, and quality of life of patients were not significant different between PCI and ODT. Performance bias and detection bias should be cautioned.