In patients with moderate and severe secondary tricuspid regurgitation (STR), the effective regurgitant orifice area (EROA), corrected using the proximal isovelocity surface area (PISA) method for tricuspid valve leaflet tethering and low TR jet velocities, has an unclear threshold for identifying high-risk patients. In this study we aimed to establish a risk-based EROA cutoff and assess the impact of right ventricular (RV) remodeling on outcomes in low-risk patients with STR according to EROA.We included 513 consecutive outpatients (age 75 ± 13 years of age, 47% male) with moderate and severe STR. Patients were categorized by spline-derived EROA threshold into low-risk (≤ 0.47 cm2) and high-risk (> 0.47 cm2) groups. The primary endpoint was a composite of heart failure hospitalization and death.Over a follow-up period of 18 ± 15 months, 195 patients reached the composite endpoint. Kaplan-Meier analysis showed a significantly higher event rate in high-risk patients (54 ± 6% vs 30 ± 7%, P 0.47 cm2 was associated with a 2-fold increased risk (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.56-2.77, P 90 mL/m (42 ± 4%), RV end-systolic volume > 46 mL/m2 (51 ± 4%), RV ejection fraction < 45% (44 ± 4%), and RV forward stroke volume/RV end-systolic volume < 0.40 (47 ± 4%).EROA independently predicts outcomes in STR. For low-risk patients according to EROA values, evaluating RV function and RV-pulmonary artery coupling enhances risk stratification.