AIMS: Tricuspid regurgitation (TR) was long forgotten until recent studies alerting on its prognostic impact. Cardiac output (CO) is the main objective of heart mechanics. We sought to compare clinical and echocardiographic data of patients with TR from inclusion to 1-year follow-up according to initial CO. METHODS AND RESULTS: Patients with isolated secondary TR and left ventricular ejection fraction (LVEF) ≥40% were prospectively included. All patients had a clinical and echocardiographic evaluation at baseline and after 1 year. Echocardiographic measurements were centralized. The patients were partitioned according to their CO at baseline. The primary outcome was all-cause death. Ninety-five patients completed their follow-up. The majority of patients had normal CO (n = 64, 67.4%), whereas 16 (16.8%) patients had low-CO and 12 (12.6%) had high-CO. right ventricular function was worse in the low-CO group but with improvement at 1 year (30% increase in tricuspid annular plane systolic excursion). LVEF and global longitudinal strain were significantly worse in the low-CO group. Overall, 18 (19%) patients died during follow-up, of which 10 (55%) patients had abnormal CO. There was a U-shaped association between CO and mortality. Normal CO patients had significantly better survival (87.5% vs. 62.5% and 66.67%) in the low- and high-CO groups, respectively, even after adjustment (heart rate 2.23 for the low-CO group and 9.08 for high-CO group; P = 0.0174). CONCLUSION: Significant isolated secondary TR was associated with 19% of mortality. It is also associated with higher long-term mortality if CO is abnormal, suggesting a possible role for evaluating better and selecting patients for intervention.