Background: Surgical management of symptomatic neonates with Tetralogy of Fallot (TOF) is controversial. Either primary surgical repair (EPSR) in neonates with TOF or a staged palliation with initial palliative intervention (PI). Aim: Compare outcomes of neonates with TOF who had EPSR and those who had PI. Materials and Methods: The study utilized the US National Inpatient Sample dataset for the years 2000 to 2018. Patients with EPSR and those with PI (aortic to pulmonary shunt or cardiac catheter palliative intervention) identified. Results: A total of 29,292 neonates with TOF were identified; of them 1726 neonates had EPSR, 4363 had PI. Hospital mortality was similar in both groups (PI 7.4% vs EPSR 8.0%, p = 0.41). Patient in the PI group had more comorbidities; chromosomal anomalies (PI 13.2% vs. ESPR 7.8%,  p < 0.001), prematurity (PI 15.1% vs. EPSR 10.4%,  p < 0.001), and low birth weight < 2500 grams (PI 15.4% vs. EPSR 10.3%,  p < 0.001). Median length of stay and median cost of hospitalization were significantly higher in the EPSR (25 days vs. 19 days, and $312,405 vs. $191,863, respectively,  p < 0.001). Conclusion: EPSR had similar mortality to PI but comes with a higher resource utilization and complications. If we include the cumulative morbidity and resource utilization associated with a two staged repair, EPSR could be proven as a better strategy in symptomatic neonates with TOF. A prospective superiority study on symptomatic neonates with TOF randomized to either ESPR or PI is needed to further answer this question.