Background: Studies comparing clinical outcomes with intravascular ultrasound (IVUS) versus optical coherence tomography (OCT) guidance for percutaneous coronary intervention (PCI) in patients presenting with coronary artery disease, including stable angina or acute coronary syndrome, are limited. Methods: We performed a detailed search of electronic databases (PubMed, Embase, and Cochrane) for randomized controlled trials and observational studies that compared cardiovascular outcomes of IVUS versus OCT. Data were aggregated for the primary outcome measure using the random-effects model as pooled risk ratio (RR). The primary outcome of interest was major adverse cardiac events (MACE), cardiac mortality, and all-cause mortality. Secondary outcomes included myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), and stroke. Results: A total of seven studies met the inclusion criteria, comprising 5917 patients (OCT n = 2075; IVUS n = 3842). OCT-PCI versus IVUS-guided PCI comparison yielded no statistically significant results for all the outcomes; MACE (RR 0.78; 95% confidence interval [CI], 0.57–1.09; p = 0.14), cardiac mortality (RR 0.97; 95% CI, 0.27–3.46; p = 0.96), all-cause mortality (RR 0.74; 95% CI, 0.39–1.39; p = 0.35), MI (RR 1.27; 95% CI, 0.52–3.07; p = 0.60), ST (RR 0.70; 95% CI, 0.13–3.61; p = 0.67), TLR (RR 1.09; 95% CI, 0.53–2.25; p = 0.81), and stroke (RR 2.32; 95% CI, 0.42–12.90; p = 0.34). Furthermore, there was no effect modification on meta-regression including demographics, comorbidities, lesion location, lesion length, and stent type. Conclusions: In this meta-analysis, OCT-guided PCI was associated with no difference in clinical outcomes compared with IVUS-guided PCI.