Pulmonary artery wedge pressure (PAWp) as a surrogate for left atrial pressure (LAp) has been validated in patients with fully pulsatile two-ventricle circulations. This study was to validate PAWp as an accurate estimate of LAp for calculating pulmonary vascular resistance in single-ventricle patients after the bidirectional Glenn operation. A prospective study measuring direct branch pulmonary artery pressures, ipsilateral PAWp, and direct LAp to calculate pulmonary and systemic blood flows was conducted. Pulmonary vascular resistance (PVR) was calculated for each patient using the PAWp and compared to the PVR calculated by direct LAp measurements. Twenty-eight patients were enrolled; 27 were eligible for study inclusion. Ages ranged from 21 to 60 months and weights ranged from 9.5 to 20.8 kg. Underlying congenital heart defect diagnoses varied, with all patients either functionally or anatomically univentricular. Left mPAWp measured 4.4 ± 2.6, statistically different from simultaneous direct mLAp of 2.5 ± 2.4 mmHg (P < 0.001. Right mPAWp measured 4.3 ± 3.2 mmHg, statistically different from simultaneous direct mLAp of 2.8 ± 2.6 mmHg (P < 0.001. The PVR calculated using mPAWp was 1.2 ± 0.7 W.U., statistically different to 1.8 ± 0.95 W.U. using mLAp (P < 0.001). The average PVR measurement calculated using mPAWp underestimated the PVR calculated using mLAp by 0.6 W.U. It can be extrapolated that a PVR of 2.3 W.U. calculated using wedge measurements would estimate a PVR of 3 W.U. calculated using direct LA measurements. In this study, the PVR calculated using PAWp as a surrogate for LAp either equaled or underestimated the true PVR, up to 33% different. This difference is important in patients with univentricular physiology who rely on low PVR for cardiac output. Thus, based on this study, a PVR measurement of greater than 2.3 W.U. by the mPAWp method should prompt a direct LA pressure measurement, in order to more appropriately determine true surgical risk.