Left ventricular systolic function is an important indicator of clinical well-being and outcomes for patients with repaired tetralogy of Fallot (TOF). This study tested the hypothesis that left ventricular diastolic function by pulsed-wave tissue Doppler is associated with quality of life in this population. In this study, 38 subjects (age, 31.0 ± 14.1 years) with repaired TOF underwent echocardiogram and completed the Short-Form 36, version 2, a validated quality-of-life assessment, within a median of 0 days (range, 0-90 days). Available cardiovascular magnetic resonance data within 1 year after the echocardiogram were analyzed. The ratio of peak early inflow to peak early annular velocity (E/E') at the lateral mitral annulus correlated inversely with the ability to participate in usual activities without physical limitations (r = -0.37; p = 0.02), whereas the right ventricular diastolic indices were not predictive. The relation of left ventricular diastolic function to quality of life was independent of left ventricular systolic function. This may be related to adverse ventricular-ventricular interactions because lateral mitral E/E' correlated with tricuspid E/E' (r = 0.46; p = 0.008) and the right ventricular myocardial performance index (r = 0.42; p = 0.01). Pulsed-wave tissue Doppler of the mitral annulus is a useful tool in this population and may potentially identify patients in need of intervention before the development of left or right ventricular systolic dysfunction.