Purpose: To assess reproducibility (interobserver variability and agreement) of Global Work Efficiency (GWE) and left ventricular ejection fraction (LVEF), assessed by 2D-echocardiography (2-DE) and 3D-echocardiography (3-DE), in patients with acute coronary syndrome (ACS), through measurements performed by operators with different levels of experience. Methods: Echocardiographers with three levels of experience were involved in offline processing: advanced, who performed image acquisition – Reader 1 (5 years of training in 2-DE, 3 years in 3-DE); intermediate – Reader 2 (3 years of training in 2-DE, 1 year in 3-DE); beginner – Reader 3 (1 year of training in 2-DE, 3 months in 3-DE). Measurements of GWE and LVEF were performed independently. Interobserver variability and agreement between readers were compared using Bland-Altman plots, as bias and limits of agreement (LOA), and Pearson correlations. Results: 90 patients (54±9 years, 75 males) with ACS were analyzed. Comparing measurements of GWE, following bias and limits of agreement (LOA) were obtained: R1 vs R2: bias -0.6, LOA -3;2 (r=0.98, p<0.001); R2 vs R3: bias -0.3, LOA -3;5 (r=0.96, p<0.001); R1 vs R3: bias -1, LOA -5;4 (r=0.94, p<0.001). Interobserver variability and agreement of GWE were comparable with LVEF by 3-DE: R1 vs R2: bias 0.6, -2, and -1.4; LOA -3;4, -7;4, and -6;4, respectively (r=0.96, 0.91, 0.94, respectively, all p<0.001); however, for LVEF by 2-DE interobserver variability was higher, while agreement was lower. Conclusion: Reproducibility of GWE in patients after an ACS is independent of experience of the operator, and similar with the reproducibility of LVEF by 3-DE.