BACKGROUND AND AIMS: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), the effects of high-sensitivity C-reactive protein (hsCRP) on Lipoprotein(a) (Lp(a))-associated cardiovascular risk remains unclear. This study aimed to investigate the independent and combined association of Lp(a) and hsCRP with cardiovascular events in this specific population. METHODS: A total of 10,424 patients with measurements of both Lp(a) and hsCRP were included in this prospective cohort study. Cox proportional hazards models and Kaplan-Meier analysis were performed to evaluate the relationship between Lp(a), hsCRP and adverse cardiac and cerebrovascular events (MACCE; all-cause death, myocardial infarction, ischemic stroke and revascularization). RESULTS: During 5 years of follow-up, 2140 (20.5%) MACCE occurred. Elevated Lp(a) and hsCRP levels were associated with increased risks of MACCE (p<0.05). Notably, there might be a significant interaction between Lp(a) and hsCRP (P for interaction = 0.019). In the setting of hsCRP≥2 mg/L, significant higher risk of MACCE was observed with Lp(a) 15-29.9 mg/dL (HR: 1.18; 95% CI 1.01-1.39) and Lp(a) ≥30 mg/dL (HR: 1.20; 95% CI 1.04-1.39), whereas such association was attenuated when hsCRP was <2 mg/L with Lp(a) 15-29.9 mg/dL (HR: 0.94; 95% CI 0.80-1.10) and Lp(a) ≥30 mg/dL (HR: 1.12; 95% CI 0.98-1.28). Moreover, when Lp(a) and hsCRP were combined for risk stratification, patients with dual elevation of these two biomarkers had a significant higher risk of MACCE compared with the reference group (Lp(a) < 15 mg/dL and hsCRp<2 mg/L) (p<0.05). CONCLUSIONS: In patients with CAD undergoing PCI, high Lp(a) level was associated with worse outcomes, and this association might be stronger in those with elevated hsCRP concomitantly. Evaluation of Lp(a) and hsCRP together may help identify high-risk individuals for targeted intervention in clinical utility.