Background and Objective: Intensive lipid-lowering therapy serves as a core intervention to improve the long-term prognosis of patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Currently, evidence-based clarification is still required for the efficacy discrepancies and applicable populations of three first-line lipid-lowering regimens: high-intensity statin monotherapy, statin plus ezetimibe, and statin plus proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). This study aimed to systematically evaluate the impacts of these three regimens on major adverse cardiovascular events (MACE) in patients with ACS after PCI. Methods: We collected relevant randomized controlled trials (RCTs) and high-quality cohort studies on the three first-line regimens published from 2016 to 2022 worldwide. A random-effects model was adopted to analyze the risk of MACE in post-PCI ACS patients, and the therapeutic effects and sources of heterogeneity across different regimens were assessed. Results: Thirty-four studies with a total of 50,537 patients were finally included. The baseline characteristics were generally comparable between groups, and minor inter-group differences did not affect the analysis. (1) High-intensity statin significantly reduced the risk of MACE (RR = 0.52, 95% CI [0.37, 0.72], p < 0.0001), with pronounced benefits in Asian populations but no significant benefit in European and American populations. (2)          Statin combined with ezetimibe lowered the MACE risk (RR = 0.59, 95% CI [0.40, 0.86], p = 0.006), and the benefit was more significant in Asian populations and in patients with a follow-up duration of ≥12 months. (3) Statin combined with PCSK9i reduced the MACE risk (RR = 0.80, 95% CI [0.72, 0.89], p < 0.0001) with low heterogeneity, and the benefit was more prominent in Asian populations and on the basis of moderate-intensity statin. Only the high-intensity statin group presented a positive Egger test, which was a false positive driven by heterogeneity, and the pooled results were stable. Conclusion: All three intensive lipid-lowering regimens can reduce the risk of MACE in post-PCI ACS patients, with more significant benefits observed in Asian populations. Statin combined with PCSK9i shows a stable risk-reduction effect.