Purpose <p>Pyloromyotomies for infantile hypertrophic pyloric stenosis in academic centers are generally performed by pediatric surgeons (PS), while in non-specialized centers these are performed by general surgeons (GS). This cross-sectional study aims to address the paucity of data comparing the safety between PS and GS when performing a pyloromyotomy within NSQIP-P participating institutions.</p> Methods <p>Data from 2012 to 2020 was obtained from the ACS-National Surgical Quality Improvement Program Pediatric (NSQIP-P) database. All patients who underwent pyloromyotomy by GS or PS were included. Patients who underwent other concurrent procedures were excluded. Demographics and postoperative outcomes were compared. Bivariate analyses and multivariable logistic regression were performed with a P-value &lt; 0.05 being considered statistically significant.</p> Results <p>A total of 18,453 pyloromyotomies were identified. Of these, 731 (4%) of cases were performed by GS and 17,722 (96%) by PS. The analysis indicated that several patient characteristics (weight, race, ASA class, comorbidities) and intra- and post-operative characteristics (operative length and hospital length of stay) were significantly different between groups. After adjusting for known risk factors, post-operative complications, re-admission rate, mortality and rate of re-operation were statistically similar between GS and PS. General surgeons were more likely to perform the operation via an open approach compared to pediatric surgeons (Adjusted OR 1.24 for Open vs. Laparoscopic, 95% CI 1.04–1.49). No significant difference was found in conversion rates (Adjusted OR 1.45 for Conversion to Open vs. Laparoscopic, 95% CI 0.68–3.08).</p> Conclusion <p>Our findings suggest no difference in 30-day outcomes within NSQIP-P pediatric-focused institutions. However, these results may not generalize to community or non-participating hospitals due to potential misclassification of surgeon specialty and selection bias.</p> Level of Evidence <p>III.</p>