The validity and reproducibility of echocardiographic methods used to quantify mitral regurgitation (MR) in children with congenital heart disease are unknown. We evaluated the usefulness of methods used to quantify MR in children enrolled in a multicenter trial of enalapril 6 months after surgical repair of an atrioventricular septal defect (AVSD). MR severity in this trial was assessed using body surface area (BSA)-adjusted vena contracta lateral (i-VCW_lat) and anterior-posterior (i-VCW_ap) dimensions and cross-sectional area (i-VCA), regurgitant volume/BSA, regurgitant fraction, and qualitative MR grade. For each method, association with left ventricular end-diastolic volume (LVEDVz) and end-diastolic dimension (LVEDDz) z-scores and interobserver agreement were assessed. In 149 children (median age 1 year), i-VCW_lat, i-VCW_ap, and i-VCA were best associated with LVEDVz (r ² = 0.54, r ² = 0.24, and r ² = 0.46, respectively; p < 0.001 for all) and showed the highest interobserver agreement (intraclass correlation coefficient = 0.62, 0.73, and 0.68, respectively). Qualitative MR grade was also associated with LVEDVz (r ² = 0.31, p < 0.001) and showed modest interobserver agreement (kappa 0.56). Regurgitant volume/BSA and regurgitant fraction were associated with LVEDVz (r ² = 0.45 and r ² = 0.45, p < 0.001 for both) but showed poor interobserver agreement [ICC = 0.28 (n = 91) and ICC = 0.17 (n = 76), respectively], and their values were negative in 75% of subjects. In conclusion, echocardiographic assessment of MR severity after AVSD remains challenging. Among the quantitative methods used in this trial, i-VCW and i-VCA performed the best but offered little advantage compared with qualitative MR grade. The utility of regurgitant volume and fraction was severely limited by poor interobserver agreement and frequently negative values.