Objective: To evaluate the relationship between cholestasis and outcomes in medical and surgical necrotizing enterocolitis (NEC).Study design: A retrospective analysis of prospectively collected data from 1472 infants with NEC [455 medical (mNEC) and 1017 surgical (sNEC)] from the Children’s Hospital Neonatal Database.Results: The prevalence of cholestasis was lower in mNEC versus sNEC (38.2% vs 70.1%, p < 0.001). In both groups, cholestasis was associated with lower birth gestational age [mNEC: OR 0.79 (95% CI 0.68–0.92); sNEC: OR 0.86 (95% CI 0.79–0.95)] and increased days of parenteral nutrition [mNEC: OR 1.08 (95% CI 1.04–1.13); sNEC: OR 1.01 (95% CI 1.01–1.02)]. For both groups, the highest direct bilirubin was associated with the composite outcome mortality or length of stay >75th percentile [mNEC: OR 1.21 (95% CI 1.06–1.38); sNEC: OR 1.06 (95% CI 1.03–1.09)].Conclusion: Cholestasis with both medical NEC and surgical NEC is associated with adverse patient outcomes including increased mortality or extreme length of stay.