Background: Despite surgical advances, neonatal truncus arteriosus repair remains high risk and approximately 10% of patients receive perioperative extracorporeal membrane oxygenation (ECMO). We aimed to assess factors and outcomes associated with the use of perioperative ECMO in infants undergoing truncus arteriosus repair. Methods: We conducted a retrospective cohort study of patients who underwent truncus arteriosus repair between 2004 and 2019, using administrative data from the Pediatric Health Information System database. Results: We identified 1,645 neonates and infants who underwent truncus arteriosus repair at 49 centers, of which 141 (8.6%) received ECMO. Prematurity (adjusted odds ratio [aOR], 2.06; 95% CI, 1.38-3.06; P < .001), truncal valve intervention (aOR, 4.69; 95% CI, 2.56-8.59; P < .001), and interrupted aortic arch repair (aOR, 1.80; 95% CI, 0.96-3.38; P = .07) were associated with perioperative ECMO. Hospital mortality occurred in 87 of 141 (62%) patients who received ECMO compared with 77/1504 (5.1%) who did not require ECMO(aOR, 13.39; 95% CI, 8.70-20.61; P < .001). In the 1,481 patients who survived to hospital discharge, ECMO was associated with higher rates of postoperative length of stay >30 days (63% [34/54] vs 28% [400/1427]; aOR 2.65; 95% CI, 1.24-5.64, P = .012) and hospital readmission within 90 days (61% [33/54 [ vs 33% [474/1427] [; aOR, 2.66; 95% CI, 1.47-4.82; P = .001). Conclusions: Prematurity, truncal valve intervention, and interrupted aortic arch repair are important risk factors that could help predict the use of perioperative ECMO. Extracorporeal membrane oxygenation utilization is strongly associated with greater odds of hospital mortality, prolonged postoperative length of stay, and higher rates of hospital readmission in surviving patients.