We compared the effect of similar effective regurgitant orifice (ERO) areas in tricuspid regurgitation (TR) and mitral regurgitation (MR) on hemodynamics and volume overload, and examined the impact on grading of TR and MR severity. In a prospective study, 95 patients with TR in sinus rhythm were compared with 95 patients with MR in sinus rhythm matched for ERO area, age, and body surface area. We found that similar ERO area was associated with decreased volume overload in TR compared with MR. There were more women with TR than with MR, but comparison stratified by sex confirmed that regurgitant volume (RVol) was smaller in TR than in MR for similar ERO area. However, patients with systolic venous flow reversal (hepatic for TR and pulmonary for MR) had lower RVol but similar ERO area in TR compared with MR. Therefore, optimal diagnostic thresholds for severe regurgitation (maximum sum of sensitivity and specificity) in TR and MR were different for RVol (45 and 60 mL/beat, respectively) but similar for ERO area (40 mm(2)). We conclude that similar ERO areas induce less RVol in TR than in MR because of the decreased driving force in TR, but have similar consequences with regard to venous flow reversal. Therefore, a similar ERO area grading scheme can be used, and an ERO area of 40 mm(2) or greater is consistent with severe regurgitation in both TR and MR.