OBJECTS: This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups. METHODS: Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan-Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted. RESULTS: During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a) < 10 mg/dL (adjusted hazard ratio [HR]: 1.85, 95% confidence interval [CI]:1.10-3.11, P = 0.021). The RCS curve indicates that the HR for MACE appeared to increase linearly with Lp(a) levels exceeding 16.9 mg/dL. However, no similar associations were obtained in the nonDM group, with an adjusted HR value of 0.57 (Lp(a) ≥ 50 mg/dL vs. < 10 mg/dL: 95% CI 0.32-1.05, P = 0.071). Besides, compared to patients without DM and Lp(a) ≥ 30 mg/dL, the MACE risk of patients in the other three groups (nonDM with Lp(a) < 30 mg/dL, DM with Lp(a) < 30 mg/dL, and DM with Lp(a) ≥ 30 mg/dL) increased to 1.67-fold (95% CI 1.11-2.50, P = 0.013), 1.53-fold (95% CI 1.02-2.31, P = 0.041), and 2.08-fold (95% CI 1.33-3.26, P = 0.001), respectively. CONCLUSIONS: In this contemporary STEMI population, high Lp(a) levels were linked to an increased MACE risk, and very high Lp(a) levels (≥ 50 mg/dL) significantly indicated poor outcomes in patients with DM, while not for those without DM. TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.