BACKGROUND: Elevated lipoprotein(a) (Lp(a)) is a recognized independent risk factor for adverse cardiovascular outcomes, particularly in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVE: This study aims to evaluate the impact of elevated Lp(a) on major adverse cardiovascular events (MACE) in patients undergoing PCI and investigate the interplay and independent contributions of Lp(a) and traditional cardiovascular risk factors. MATERIALS AND METHODS: A prospective cohort study was conducted over two years, including 360 patients undergoing PCI. Participants were divided into high and normal groups according to their baseline Lp(a) levels. To record MACE, which includes myocardial infarction, stroke, repeat revascularization, and cardiovascular mortality, clinical, demographic, and laboratory data were gathered, and patients were monitored for 24 months. The association between Lp(a) levels, MACE, and conventional risk variables was examined using Cox proportional hazards models. RESULTS: Those with normal Lp(a) (18.69 ± 5.39 mg/dL) had substantially lower rates of MACE, such as myocardial infarction (HR = 1.89, p = 0.002), stroke (HR = 1.48, p = 0.039), and cardiovascular mortality (HR = 2.23, p = 0.001), than those with raised Lp(a) (79.31 ± 35.13 mg/dL). The raised group had a considerably reduced event-free survival rate (74.13% vs. 91.76%, p <
0.001). The raised group was more likely to have traditional risk factors, including diabetes and hypertension, which increased the negative consequences. CONCLUSION: Elevated Lp(a) significantly increases the risk of MACE in PCI patients, and this risk is further modulated by the presence of traditional cardiovascular risk factors, emphasizing the need for comprehensive risk stratification.