Background and Aims: This study investigates the feasibility of performing anorectal surgery in neonates in a prone position via epidural anesthesia and sedation without an instrumented airway. Methods: Twenty infants, scheduled for surgery for anorectal malformations, were included in this study. The primary endpoint was the success of the anesthesia method without invasive airway manipulation after skin incision, and secondary endpoints were defined as the need for additional opioids or sedation drugs during the perioperative period. The study was approved by the Ethics Committee of the Medical University of Vienna (ref. 1133/2017—approval date 24 August 2017), and was registered in the German Clinical Trial Register (DRKS ID: DRKS00012683, approval date 15 July 2019, updated 30 July 2020). Results: The primary outcome parameter could be achieved in 95% of the cases, and 85% of the cases could be managed without additional opioids (secondary outcome parameter). Only one infant (5%) needed endotracheal intubation due to laryngospasm during prone positioning. Conclusions: Surgery for infantile anorectal malformations in a prone position is possible with epidural anesthesia and sedation without an instrumented airway.