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In an era of rapidly expanding and evolving 3-dimensional echocardiographic (3DE) technology, 1 of the issues facing the 3DE quantification of chamber volumes and function is that different software vendors use different methodologies and algorithms. The aim of this study was to evaluate the comparability and reproducibility of 3DE direct volumetric and speckle-tracking methods for left ventricular (LV) and left atrial (LA) chamber quantification. A total of 120 subjects (mean age 53 ± 17 years, 65% men), including 88 unselected patients and 32 healthy volunteers, underwent 3DE acquisitions and analysis using direct volumetric and speckle-tracking methods successively. Measurements of LV and LA volumes and LV function were compared between the 2 3DE methods. Additionally, intraobserver and interobserver reproducibility was assessed in 40 randomly selected patients. Measurements of LV end-diastolic volume, end-systolic volume, and ejection fraction by 3DE direct volumetric and 3DE speckle-tracking methods were comparable, with good correlations (r = 0.98, r = 0.98, and r = 0.87, respectively), small biases, and narrow limits of agreement (−1 ± 8 ml, −1 ± 8 ml, and 0 ± 6%, respectively). For measurements of LA end-systolic volume and end-diastolic volume, similar correlations (r = 0.96 for both), small biases, and narrow limits of agreement (−2 ± 6 and −1 ± 5 ml, respectively) were found between the 2 methods. Intraobserver and interobserver reproducibility for LV and LA quantification were comparable for the 2 methods. In conclusion, 3DE direct volumetric and speckle-tracking methods give comparable and reproducible quantification of LV and LA volumes and function, making interchangeable application a viable option in daily clinical practice. [Copyright &y& Elsevier]