BACKGROUND: Lipoprotein(a) [Lp(a)] was positively associated with recurrent ischemic events in patients with acute coronary syndrome (ACS). This study was performed to investigate the effect of Lp(a) levels on outcomes of dual antiplatelet therapy (DAPT) > 1 year versus DAPT ≤ 1 year after percutaneous coronary intervention (PCI) in this population. METHODS: A total of 4,357 ACS patients who were event-free at 1 year after PCI were selected from the Fuwai PCI Registry, and patients were stratified into four groups according to DAPT duration (≤ 1 year vs. > 1 year) and Lp(a) levels (≤ 30 mg/dL vs. > 30 mg/dL). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of cardiac death, myocardial infarction or stroke. RESULTS: After 2.4-year follow-up, the incidence of MACCE (HRadjusted 0.284, 95% CI 0.115-0.700; HRIPTW 0.351, 95% CI 0.164-0.751) were significantly reduced in DAPT > 1 year group than that in DAPT ≤ 1 year group in individuals with elevated Lp(a) levels. However, in individuals with normal Lp(a) levels, no statistically difference was found between these two groups in terms of MACCE, although the risks of all-cause death and definite/probable stent thrombosis were lower in DAPT > 1 year group. Notably, the risk of clinically relevant bleeding did not statistically differ between these two groups in individuals with different Lp(a) levels. CONCLUSIONS: This study firstly demonstrated that extended DAPT (> 1 year) was statistically associated with lower risk of ischemic events in ACS patients with elevated Lp(a) levels after PCI, whereas this association was not found in individuals with normal Lp(a) levels.