Background: Subanesthetic intravenous (IV) ketamine acts as an analgesic and has opioid-sparing effects, particularly for acute postoperative pain; however, its effectiveness in children is understudied. The primary aim of this study was to evaluate the non-inferiority of subanesthetic IV ketamine vs. caudal bupivacaine for postoperative analgesia in children undergoing infraumbilical surgery.Methods: Children aged < 6 years were enrolled in this single-blind study and randomized to receive either subanesthetic IV ketamine (0.3 mg/kg) or caudal 0.125% bupivacaine (1 ml/kg) along with general anesthesia. Postoperative pain was assessed using the FLACC scale at 30 minutes and 1, 2, 3, and 6 h post-operation. Intra- and postoperative opioid consumption, time to extubation, postoperative vomiting, agitation, sedation, and inflammatory markers were also assessed.Results: Altogether, 141 children completed the study (ketamine group: n = 71, caudal group: n = 70) The cumulative proportion of children without significant postoperative pain (FLACC score < 4) in the first 6 h post-surgery was 45.1% in the ketamine group vs. 72.9% in the caudal group (P < 0.001). More children in the ketamine group required an additional dose of intraoperative fentanyl (33.8% vs. 5.7%, P < 0.001) and postoperative tramadol (54.9% vs. 27.1%, P < 0.001). However, postoperative agitation, sedation, and other secondary outcomes were similar between the groups.Conclusions: Subanesthetic ketamine is inferior to caudal bupivacaine for postoperative analgesia in children aged < 6 years undergoing infra-umbilical surgeries; however, other postoperative outcomes are similar.