Background: Pulse pressure variation derived from the varied pulse contour method is based on heart-lung interaction during mechanical ventilation. It has been shown that pulse pressure variation is predictive of fluid responsiveness in children undergoing surgical repair of ventricular septal defect. Right ventricle compliance and pulmonary vascular capacitance in children with tetralogy of Fallot are underdeveloped as compared to those in ventricular septal defect. We hypothesized that the difference in the right ventricle-pulmonary circulation in the two groups of children would affect the heart-lung interaction and therefore pulse pressure variation predictivity of fluid responsiveness following cardiac surgery. Methods: Infants undergoing complete repair of ventricular septal defect (n=38, 1.05±0.75 years) and tetralogy of Fallot (n=36, 1.15±0.68 years) clinically presenting with low cardiac output were enrolled. Fluid infusion with 5% albumin or fresh frozen plasma was administered. Pulse pressure variation was recorded using pressure recording analytical method along with cardiac index before and after fluid infusion. Patients were considered as responders to fluid loading when cardiac index increased ≥15%. Receiver operating characteristic curves analysis was used to assess the accuracy and cutoffs of pulse pressure variation to predict fluid responsiveness. Results: The pulse pressure variation values before and after fluid infusion were lower in tetralogy of Fallot children than those in ventricular septal defect children (15.2±4.4% vs 19.3±4.4%, P<.001; 11.6±3.8 vs 15.4±4.3%, P<.001, respectively). In ventricular septal defect children, 27 were responders and 11 nonresponders. Receiver operating characteristic curve area was 0.89 (95% confidence interval, 0.77-1.01) and cutoff value 17.4% with a sensitivity of 0.89 and a specificity of 0.91. In tetralogy of Fallot children, 26 were responders and 10 were nonresponders. Receiver operating characteristic curve area was 0.79 (95% CI, 0.64-0.94) and cutoff value 13.4% with a sensitivity of 0.81 and a specificity of 0.80. Conclusion: Pulse pressure variation is predictive of fluid responsiveness in ventricular septal defect and tetralogy of Fallot patients following cardiac surgery. © 2017 John Wiley & Sons Ltd