BackgroundWe aimed to assess the characteristics, management and long-term prognosis of a cohort of patients with multiple valvular disease, focusing on the context of severe mitral or aortic disease with concomitant significant tricuspid regurgitation (TR). MethodsAfter using a propensity score matching for age, 975 patients with ≥ moderate TR, diagnosed at our centers from 2012 to 2020, were included and divided in four groups, including isolated TR patients as reference group. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization + any valvular intervention. ResultsPatients with isolated TR (356, 37 %) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). Patients with severe mitral regurgitation (MR) + TR (466, 48 %) showed higher rates of concomitant coronary artery disease, advanced functional class symptoms and larger left atrial volumes. Severe aortic stenosis (AS) patients (131, 13 %) were older, with more comorbidities and lower LVEF. Patients with severe aortic regurgitation and TR (22, 2 %) were younger, with larger LV dimensions and higher pulmonary arterial pressures.After a median follow-up of 2.8 years, both endpoints were univariably more frequent in patients with severe AS + TR (all p < 0.001), but after comprehensive adjustment difference in the primary endpoint became insignificant, underscoring the serious outcomes of all significant TR groups significantly. Overall, in 44 (5 %) patients tricuspid intervention was performed, with no differences between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment. ConclusionsIn the context of severe left-sided VD, concomitant significant TR is common, and each subtype presents with different clinical and echocardiographic features: patients with severe AS and TR have considerable worse prognosis, although comprehensive adjustment reflected the poor outcomes affecting all types of patients with significant TR. In this scenario, TR was profoundly undertreated.