Description: Background— Multiple echocardiographic methods are used to measure left ventricular size and function. Clinical management is based on individual evaluations and longitudinal trends. The Pediatric Heart Network VVV study (Ventricular Volume Variability) in pediatric patients with dilated cardiomyopathy has reported reproducibility of several of these measures, and how disease state and number of beats impact their reproducibility. In this study, we investigated the impact of observer and sonographer variation on reproducibility of dimension, area, and volume methods to determine the best method for both individual and sequential evaluations. Methods and Results— In 8 centers, echocardiograms were obtained on 169 patients prospectively. During the same visit, 2 different sonographers acquired the same imaging protocol on each patient. Each acquisition was analyzed by 2 different observers; first observer analyzed the first acquisition twice. Intraobserver, interobserver, interacquisition, and interobserver-acquisition (different observers and different acquisition) reproducibility were assessed on measurements of left ventricular end-diastolic dimension, area, and volume. Left ventricular shortening fraction, ejection fraction, mass, and fractional area change were calculated. Percent difference was calculated as (interobservation difference/mean) x 100. Interobserver reproducibility for both acquisitions was better for both volume and dimension measurements ( P ≤0.002) compared with area measurements, whereas intraobserver, interacquisition (for both observers), and interobserver-acquisition reproducibilities (for both observer-acquisition sets) were best for volume measurements ( P ≤0.01). Overall, interobserver-acquisition percent differences were significantly higher than interobserver and interacquisition percent differences ( P 〈0.001). Conclusions— In pediatric patients with dilated cardiomyopathy, compared with dimension and area methods, left ventricular measurements by volume method have the best reproducibility in settings where assessment is not performed by the same personnel. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00123071.