Objective ·To evaluate the relevant risk factors and pathophysiological mechanisms of moderate-to-severe secondary tricuspid regurgitation (STR) in acute ST-segment elevation myocardial infarction (STEMI) patients using cardiac magnetic resonance (CMR) imaging. Methods ·A total of 729 STEMI patients who underwent percutaneous coronary intervention (PCI) at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from August 2013 to June 2023 were analyzed. All patients underwent both CMR and transthoracic echocardiography (TTE) examinations within 2‒7 d post-PCI. Patients were stratified into two groups based on TTE findings: significant STR (moderate-to-severe) and non-significant STR (mild or absent). Clinical characteristics, CMR parameters, and the incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) were compared between the groups. Univariate and multivariate Logistic regression analyses were performed to identify independent predictors of significant STR. Results ·Of the 729 enrolled STEMI patients, 53 (7.3%) developed significant STR. Compared to the non-significant STR group (n=676), patients with significant STR were older, had a lower proportion of males, and had a lower prevalence of hyperlipidemia (all P<0.05). Survival analysis revealed a significantly higher cumulative incidence of MACCEs in the significant STR group than in the non-significant STR group (log-rank P<0.001). CMR analysis revealed that the significant STR group exhibited more pronounced left ventricular remodeling and myocardial strain impairment, characterized by an increased left ventricular end-systolic volume index (LVESVi) and reduced left ventricular ejection fraction (LVEF). Additionally, this group showed significantly decreased left ventricular global radial strain (LV-GRS), the absolute value of left ventricular global circumferential strain (LV-GCS), the absolute value of radial peak early diastolic strain rate (rPEDSR), and circumferential peak early diastolic strain rate (cPEDSR) (all P<0.05). Multivariate Logistic regression analysis identified LVESVi (OR=1.030, 95%CI 1.011‒1.049, P=0.002), LVEF (OR=0.963, 95%CI 0.940‒0.986, P=0.002), LV-GRS (OR=0.953, 95%CI 0.913‒0.994, P=0.026), and LV-GCS (OR=1.091, 95%CI 1.011‒1.178, P=0.025) as independent factors associated with significant STR, all of which demonstrated good discriminative performance (all AUC>0.83). Conclusion ·STR occurring acutely in STEMI patients is significantly associated with adverse clinical outcomes. Left ventricular structural remodeling and dysfunction are the key pathophysiological basis for its development. CMR-derived parameters provide crucial evidence for early identification and risk stratification of significant STR.