OBJECTIVES: Superior vena cava oxygen saturation (SVC O2) monitoring is well described for early detection of hemodynamic deterioration after neonatal cardiac surgery but inferior vena cava vein oxygen saturation (IVC O2) monitoring data are limited. DESIGN: Retrospective cohort study of 118 neonates with congenital heart disease (52 single ventricle) from February 2008 to January 2014. SETTING: Pediatric cardiac ICU. PATIENTS: Neonates (< 30 d) with concurrent admission IVC O2and SVC O2measurements after cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary aim was to correlate admission IVC O2and SVC O2. Secondary aims included: correlate flank or cerebral near-infrared spectroscopy with IVC O2and SVC O2, respectively, and exploratory analysis to evaluate associations between oximetry data and a composite adverse outcome defined as any of the following: increasing serum lactate or vasoactive support at 2 hours post-admission, cardiac arrest, or mortality. Admission IVC O2and SVC O2correlated (r = 0.54; p < 0.001). However, IVC O2measurements were significantly lower than paired SVC O2(mean difference, -6%; 95% CI, -8% to -4%; p < 0.001) with wide variability in sample agreement. Logistic regression showed that each 12% decrease in IVC O2was associated with a 12-fold greater odds of the composite adverse outcome (odds ratio [OR], 12; 95% CI, 3.9-34; p < 0.001). We failed to find an association between SVC O2and increased odds of the composite adverse outcome (OR, 1.8; 95% CI, 0.99-3.3; p = 0.053). In an exploratory analysis, the area under the receiver operating curve for IVC O2and SVC O2, and the composite adverse outcome, was 0.85 (95% CI, 0.77-0.92) and 0.63 (95% CI, 0.52-0.73), respectively. Admission IVC O2had strong correlation with concurrent flank near-infrared spectroscopy value (r = 0.74; p < 0.001). SVC O2had a weak association with cerebral near-infrared spectroscopy (r = 0.22; p = 0.02). CONCLUSIONS: In postoperative neonates, admission IVC O2and SVC O2correlate. Lower admission IVC O2may identify a cohort of postsurgical neonates at risk for low cardiac output and associated morbidity.