Quantitative assessment of ventricular function in patients with congenital heart disease is often challenging due to distorted ventricular geometry. A myocardial performance index (MPI) has been reported in adults and children that is a Doppler-derived nongeometric measure of ventricular function. The MPI measures the ratio of isovolumic time intervals (isovolumic contraction time and isovolumic relaxation time) to ventricular ejection time. The effects of altered ventricular preload or afterload on the MPI have yet to be determined. This study assesses the impact of altered preload or afterload on right ventricular (RV) function and the RV MPI in the clinical setting of congenital heart disease. Patient groups were compared with normal pediatric and adult populations before and after repair of their congenital heart lesion. Patients with large atrial septal defects (ASDs) represented the clinical setting of increased ventricular preload, whereas patients with isolated pulmonary valve stenosis represented increased RV afterload. Patients with congenitally corrected transposition of the great arteries (CC-TGA) with severe left atrioventricular valve regurgitation represented a combined increase in RV preload and afterload. The RV MPI in 152 normal children (ages 3 to 18 years) and 37 adults (ages 18 to 51 years) was 0.32 +/- 0.03 and 0.28 +/- 0.04, respectively. In pediatric patients (n = 45) and adult patients (n = 40) with ASD, the RV MPI was 0.35 +/- 0.09 (p = NS) and 0.38 +/- 0.04 (p < 0.01 compared with normal adults), respectively. Patients with pulmonary stenosis (n = 21, ages 1 day to 19 years) had a RV MPI of 0.32 +/- 0.06 (p = NS). CC-TGA patients had a RV MPI of 0.72 +/- 0.17 (p < 0.001). No significant change in the RV MPI was seen in any postoperative patient group despite relief of RV volume or pressure overload. Thus, the MPI is a quantitative measure of RV performance that is appears to be relatively independent of changes in preload or afterload in the clinical setting.