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Hemolysis is a known complication of pediatric extracorporeal membrane oxygenation associated with renal failure and mortality. We sought to identify predictors of hemolysis in pediatric extracorporeal membrane oxygenation patients and determine its influence on outcomes.Retrospective, single-center study.Urban, quaternary care center pediatric and neonatal ICU.Ninety-six patients requiring extracorporeal membrane oxygenation.None.Daily measurements of plasma-free hemoglobin were obtained while patients were on extracorporeal membrane oxygenation. Patients with a prior extracorporeal membrane oxygenation run, on extracorporeal membrane oxygenation for less than 24 hours, or without complete medical records were excluded from the study. Ninety-six patients met inclusion criteria, of which, 25 patients (26%) had plasma-free hemoglobin greater than 30 mg/dL. Of those patients, 15 of 25(60%) had plasma-free hemoglobin greater than 50 mg/dL, and 21 of 25(84%) occurred during the first 7 days on extracorporeal membrane oxygenation. Compared with patients without hemolysis, those with hemolysis were younger (0.2 mo [0.06–3.2 mo] vs 8.2 mo [0.6–86 mo]; p < 0.001), had a higher pericannulation international normalized ratio (3.9 [3.5–5.5] vs 2.6 [1.8–3.7]; p = 0.003), lower pericannulation platelet count (33 × 103/μL [22–42 × 103/μL] vs 61 × 103/μL [38–86 × 103/μL]; p < 0.001), and had a less negative inlet pressure (–3.5 mm Hg [–14 to 11.5 mm Hg] vs –19 mm Hg [–47 to 0 mm Hg]; p = 0.01). A greater proportion of patients with hemolysis had a heparin assay less than 0.2 mg/dL (50% vs 17%; p = 0.001) and had fluid removal via slow continuous ultrafiltration (32% vs 6%; p < 0.001). Patients with hemolysis had increased risk of in-hospital mortality (odds ratio 10.0; 95% CI 3.4–32; p < 0.001). On multivariable analysis, continuous ultrafiltration (odds ratio, 8.0; 95% CI, 1.9–42; p = 0.007) and pericannulation international normalized ratio greater than 3.5 (odds ratio, 7.2; 95% CI, 2.3–26; p = 0.001) were significantly associated with hemolysis.Hemolysis is a common complication of pediatric extracorporeal membrane oxygenation. We found that patients with hemolysis (plasma-free hemoglobin > 30 mg/dL) had a 10-fold increase in in-hospital mortality. In our study cohort, hemolysis was associated with continuous ultrafiltration use, but not continuous renal replacement therapy. Additionally, our results suggest that the degree of coagulopathy (international normalized ratio > 3.5) at the time of cannulation influences hemolysis. Additional prospective studies are necessary to define further strategies to prevent hemolysis and improve outcomes in pediatric extracorporeal membrane oxygenation patients.