Objectives We sought to compare the clinical outcomes between culprit-only percutaneous coronary intervention (PCI) versus multivessel PCI (MV-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) accompanied by chronic total occlusion (CTO) in the non-infarct-related artery(non-IRA). Design Studies that compared culprit-only PCI versus MV-PCI in patients with STEMI accompanied by CTO in the non-IRA were included. Random odds ratio (OR) and 95% confidence interval (CI) were calculated. Results Eight studies with 2,259 patients were included. The results suggested that in patients with STEMI accompanied by CTO in the non-IRA, culprit-only PCI was associated with higher risks of all-cause mortality (OR: 2.89; 95% CI: 2.09–4.00; I 2 = 0.0%), cardiac death (OR: 3.12; 95% CI: 2.05–4.75; I 2 = 16.8%), stroke (OR: 2.80; 95% CI: 1.04–7.53; I 2 = 0.0%), major adverse cardiovascular event (MACE; OR: 2.06; 95% CI: 1.39–3.06; I 2 = 54.0%), and heart failure (OR: 1.99; 95% CI: 1.22–3.24; I 2 = 0.0%) compared with staged MV-PCI, which were mainly derived from retrospective studies. No differences were observed in myocardial infarction or revascularization. Pooled multivariable adjusted results consistently indicated that staged MV-PCI was superior to culprit-only PCI. Conclusions For patients with STEMI accompanied by CTO in the non-IRA, staged MV-PCI may be better compared with culprit-only PCI due to potential reduced risks of all-cause mortality, cardiac death, stroke, MACE, and heart failure. Meanwhile, further randomized trials are warranted to confirm or refute our findings.