Chronic pressure-overload induces right ventricular (RV) adaptation to maintain RV–pulmonary arterial (PA) coupling. RV remodeling is frequently associated with secondary tricuspid regurgitation (TR) which may accelerate uncoupling. Our aim is to determine whether the non-invasive analysis of RV–PA coupling could improve risk stratification in patients with secondary TR. A total of 1,149 patients (median age 72[IQR, 63 to 79] years, 51% men) with moderate or severe secondary TR were included. RV–PA coupling was estimated using the ratio between two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). The risk of all-cause mortality across different values of TAPSE/PASP was analyzed with a spline analysis. The cut-off value of TAPSE/PASP to identify RV–PA uncoupling was based on the spline curve analysis. At the time of significant secondary TR diagnosis the median TAPSE/PASP was 0.35 (IQR, 0.25 to 0.49) mm/mm Hg. A total of 470 patients (41%) demonstrated RV–PA uncoupling (<0.31 mm/mm Hg). Patients with RV–PA uncoupling presented more frequently with heart failure symptoms had larger RV and left ventricular dimensions, and more severe TR compared to those with RV–PA coupling. During a median follow-up of 51 (IQR, 17 to 86) months, 586 patients (51%) died. The cumulative 5-year survival rate was lower in patients with RV–PA uncoupling compared to their counterparts (37% vs 64%, p < 0.001). After correcting for potential confounders, RV–PA uncoupling was the only echocardiographic parameter independently associated with all-cause mortality (HR 1.462; 95% CI 1.192 to 1.793; p < 0.001). In conclusion, RV–PA uncoupling in patients with secondary TR is independently associated with poor prognosis and may improve risk stratification.