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Three-dimensional (3D) echocardiography directly assesses right ventricular (RV) volumes without geometric assumptions, despite the complex shape of the right ventricle, and accordingly is more accurate and reproducible than the two-dimensional methodology, which is able to measure only surrogate parameters of RV function. Volumetric analysis has been hampered by frequent inability to clearly visualize RV endocardium, especially the RV free wall, in 3D echocardiographic images. The aim of this study was to test the hypothesis that RV contrast enhancement during 3D echocardiographic imaging would improve the accuracy of RV volume and function analysis.Thirty patients with a wide range of RV size and function and image quality underwent transthoracic 3D echocardiography with and without contrast enhancement and cardiovascular magnetic resonance imaging on the same day. RV end-diastolic and end-systolic volumes and ejection fraction were measured from contrast-enhanced and nonenhanced 3D echocardiographic images and compared with cardiovascular magnetic resonance reference values using linear regression and Bland-Altman analyses. Blinded repeated measurements were performed to assess measurement variability.RV contrast enhancement was feasible in all patients. RV volumes obtained both with and without contrast enhancement correlated highly with cardiovascular magnetic resonance (end-diastolic volume, r = 0.90 and r = 0.92; end-systolic volume, r = 0.92 and r = 0.94, respectively), but the correlation for ejection fraction was better with contrast (r = 0.87 vs r = 0.70). Biases were smaller with contrast for all three parameters (end-diastolic volume, −16 ± 23 vs −36 ± 25 mL; end-systolic volume, −10 ± 16 vs −23 ± 18 mL; ejection fraction, −0.7 ± 5.5% vs −2.7 ± 8.1% of the mean measured values), reflecting improved accuracy. Also, measurement reproducibility was improved by contrast enhancement.Contrast enhancement improves the visualization of RV endocardial borders, resulting in more accurate and reproducible 3D echocardiographic measurements of RV size and function. This approach may be particularly useful in patients with suboptimal image quality.We hypothesized that contrast enhancement during 3D echocardiographic imaging would improve the accuracy of RV volume and function analysis.This hypothesis was tested by comparing measurements obtained from nonenhanced and contrast-enhanced images against cardiac magnetic resonance reference images.Contrast enhancement improved the visualization of RV endocardial borders, resulting in more accurate and more reproducible measurements.This approach may be particularly useful in patients with suboptimal image quality.Abbreviations: 2D = Two-dimensional; 3D = Three-dimensional; CMR = Cardiovascular magnetic resonance; EDV = End-diastolic volume; ESV = End-systolic volume; LV = Left ventricular; RV = Right ventricular; RVEF = Right ventricular ejection fraction; RVOT = Right ventricular outflow tract.