Introduction: A large proportion of postoperative mortality after pediatric surgery occurs among neonates with specific high-risk diagnoses. The extent to which there is hospital-level mortality variation among patients with these diagnoses and whether this variation is associated with differences in failure to rescue (FTR) is unclear. Methods: The Pediatric Health Information System® database (2012–2020) was used to identify patients who underwent surgery for eight high-risk neonatal diagnoses: gastroschisis; volvulus; necrotizing enterocolitis; intestinal atresia; meconium peritonitis; tracheoesophageal fistula; congenital diaphragmatic hernia; perinatal intestinal perforation. Hospitals were stratified into tertiles of reliability adjusted inpatient mortality rates (lower than average mortality— tertile 1 [T1]; higher than average mortality—tertile 3 [T3]). Multivariable hierarchical regression was used to evaluate the association between hospital-level, reliability adjusted mortality and FTR Results: Overall, 20,838 infants were identified across 48 academic, pediatric hospitals. Adjusted hospital mortality rates ranged from 4.0% [95% CI, 0.0–8.2] to 16.3% [12.2–20.4]. Median case volume (range, 80–1238) and number of NICU beds (range, 24–126) were not significantly different across hospital tertiles. Compared to the hospitals with the lowest postoperative mortality (T1), the odds of FTR was significantly higher in hospitals with the highest (T3) postoperative mortality (OR 1.97 [1.50–2.59]). Conclusions: Significant variation in neonatal hospital mortality for high-risk diagnoses does not appear to be explained by hospital structural characteristics. Rather, difference in FTR suggest QI interventions targeting early recognition and management of postoperative complications could improve surgical quality and safety for high-risk neonatal care.