This study aimed to test the hypothesis that right ventricular (RV) volume overload may result in left ventricular (LV) systolic dysfunction through induction of LV systolic dyssynchrony after tetralogy of Fallot (TOF) repair. Sixty patients with TOF repair were studied at 14.3 +/- 7.2 years after TOF repair. Real-time 3-dimensional echocardiographic data sets were acquired for measurement of LV and RV volumes and derivation of ejection fractions and pulmonary regurgitant volume. The LV systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume using a 16-segment model. The results were compared with those of 29 healthy controls. LV SDI was significantly higher in patients than controls (7.4% +/- 2.0% vs 3.0% +/- 0.9%, p <0.001). The prevalence of LV mechanical dyssynchrony (SDI >4.7%) in patients was 93% (95% confidence interval 87% to 100%). The time to minimum regional volume was significantly longer in all of the 6 basal segments and the midposterior segment (all p <0.05) in patients than controls. Multivariate analysis identified RV end-diastolic volume (beta = 0.58, p <0.001), LV ejection fraction (beta = -0.38, p <0.001), and LV end-diastolic volume (beta = 0.26, p = 0.002) as significant correlates of LV SDI. In conclusion, in patients after TOF repair, RV volume overload has a negative effect on LV systolic function through induction of global LV mechanical dyssynchrony.