Previous studies using speckle-tracking echocardiography (STE) for quantifying the functions of the right and left ventricles (RV and LV, respectively) in the presence of percutaneous atrial septal defect (ASD) closure have focused on the peak systolic strain (PSS). This study investigated changes in the mechanical dyssynchrony of ventricular contraction before and after ASD closure, issues that have been little addressed in the literature. Thirty-one adults with ASD were studied using two-dimensional STE before and 24 h after ASD closure. Thirty-one healthy age- and sex-matched subjects were recruited as controls. Global and segmental PSS values from the longitudinal, circumferential, and radial directions were analyzed. The time to peak systolic strain (PSST) and the standard deviation of the time to peak strain (SDT) among segments in each direction were calculated, to investigate the inter- and intra-ventricular mechanical dyssynchrony in these patients and improvements after closure. Compared to the control group, patients with ASD had higher RV free-wall longitudinal systolic strain, with increased PSST and SDT. The SDT values of the LV longitudinal and circumferential strains were also increased. By 24 h after ASD closure, the RV free-wall longitudinal strain and its PSST and SDT had reverted to normal levels. The LV circumferential strain was increased, and its SDT was decreased. The contraction period of the RV and myocardial contraction dyssynchrony in the RV and LV were increased in ASD patients. The inter- and intra-ventricular mechanical utilities were improved after percutaneous closure of the ASD.