OBJECTIVE: To assess the efficacy and safety of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in reducing major adverse cardiovascular events (MACE) in statin-intolerant patients, focusing on low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular outcomes. METHODS: A systematic review and meta-analysis were conducted according to the PRISMA guidelines. Randomised control trails (RCTs) and observational studies from PubMed, Cochrane Library, and Web of Science databases were included. Independent reviewers extracted the data, and the analyses were performed using fixed- and random-effects models. Heterogeneity was evaluated using the I RESULTS: Fifteen studies involving 69-18 924 participants were included. PCSK9 inhibitors reduced LDL-C levels by 50-70% and lowered the risk of MACE by 12% (OR 0.88). Minimal heterogeneity (I CONCLUSION: PCSK9 inhibitors are effective and safe alternatives for LDL-C reduction and cardiovascular risk mitigation in patients with statin intolerance. Their efficacy, favorable safety profile, and consistency across studies highlight their potential for managing dyslipidemia, particularly in high-risk groups. Further research on long-term outcomes is required.