Introduction Radiation therapy targets tumor tissue and requires children to lay still, which often necessitates procedural sedation. Historically anesthesiologists provided procedural sedation, but pediatric critical care physicians now regularly administer sedation to children outside the operating room. Procedural sedation for radiation therapy poses unique challenges. This study’s objective was to evaluate the efficacy and safety of repeated sedations for radiation therapy performed by pediatric critical care physicians. Methods We performed a single-center, retrospective case series of children who received procedural sedation for radiation therapy by pediatric critical care physicians. The primary outcome was the success rate, defined as completion of the sedation and radiation treatment. Secondary outcomes included type of medication, dosing, tolerance, and complications requiring intervention. Results In our sample, 55 patients underwent 1174 sedation instances (mean 19.8 sedations per patient). Patients had a mean age of 4.7 years (SD 3.4), and a mean weight of 20.2 kg (SD 11.9). All patients had an ASA of 2 (74.5%) or 3 (25.5%). All patients had either a brain tumor (49.1%) or a solid tumor that was non-mediastinal (50.9%). The success rate of sedations was 99.8% (1172/1174). The mean duration of sedation was 30.7 min (SD 12.4). All sedations included propofol as a first agent with a mean bolus 3.3 mg/kg (SD 1.4) and a mean drip rate 148.7 mcg/kg/min (SD 39.7). 4.4% of sedations required a second agent (ketamine or dexmedetomidine). There was no significant effect of repeated sedation with regards to the medication amount received (p=0.97). 0.2% of sedations had laryngospasm. No patients required bag-mask ventilation, intubation, or chest compressions; no patients died. ­ Conclusion Pediatric critical care physicians can perform procedural sedation for radiation therapy successfully and safely.