Abstract Background Functional mitral regurgitation (FMR) evaluation using effective regurgitant orifice (ERO) by echocardiography remains controversial. Given the morphology of regurgitant jets in FMR, determination of ERO using three-dimensional transesophageal echocardiography (3D-TEE) may be more accurate. However, a clear threshold for this parameter has not been defined. Purpose Our aim is to evaluate the prognostic value of 3D-ERO in FMR. Methods All patients with at least moderate FMR who underwent 3D-TEE in a tertiary center between 2016 and 2020 were retrospectively selected. Echocardiographic variables by transthoracic and transesophageal, as well as demographic and clinical history variables, were collected. A combined event of urgent hospital admission or death was considered. Variables statistically associated with the event were included in multivariate analysis. Results 112 patients (74 men (66.1%), mean age 72.3±10.9 years) were finally included. The most frequent etiology of FMR was ventricular dysfunction (61.6%), followed by annular dilation (23.2%) and posterior leaflet restriction (15.2%). The mean 3D-ERO was 0.53±0.25 cm2 and mean ejection fraction was 40.7±14.2%. At diagnosis, 49 patients (43.8%) were not receiving diuretics, 63 (56.2%) had atrial fibrillation/flutter, 60.3% permanent. FMR was treated in 54 patients (48.2%), 61,1% percutaneously. During a follow-up of 36 14-54 months, 50 (44,6%) patients were urgently hospitalized (mean 1.9±2.8 admissions) and 49 (43,8%) died, received a heart transplant or LVAD. 3D-ERO was significantly associated with the occurrence of the event (0.55 vs 0.41; p=0.02). Additionally, 3D-ERO was associated with mitral intervention (0.58 vs 0.47 cm2; p=0.01) and had a trend towards death from any cause (0.56 vs 0.5 cm2; p=0.098). The prognostic capacity of 3D-ERO for the combined event was determined using an ROC curve (Figure). An AUC of 0.67 (95% CI 0.55-0.8; p=0.01) and an optimal cutoff value of 0.45 cm2 (sensitivity 0.62, specificity 0.73) were obtained. In univariate analysis, the combined event was also associated with age (73.9 vs. 65.6 years; p=0.01), diabetes (40 vs. 13.6%; p=0.02), chronic kidney disease (42.7 vs. 13.6%; p=0.01), ischemic heart disease (59.6 vs 31,8%, p=0.02) and daily furosemide dose (39.7 vs. 13.6 mg; p<0.01). In multivariate analysis of the event, age, daily furosemide dose, ischemic heart disease and 3D-ERO were included in the final predictive model (Table). Conclusions In patients with FMR, 3D-ERO was significantly associated with the occurrence of events during follow-up, with an optimal prognostic performance cutoff point of 0.45 cm2. Furthermore, it was an independent predictor of mitral intervention and included among the predictors of urgent hospital admission or death. Therefore, 3D-ERO may be useful in risk stratification of FMR.