Background: Continuous advancements in ultrasound (US)-guided neuraxial and peripheral nerve blocks (PNB) have allowed the safe and successful use of these blocks as adjuvants to general anesthesia in pediatric patients. Objectives: This study was designed to compare the analgesic efficacy of 2 US-guided regional techniques, caudal epidural block (CEB) and subgluteal sciatic nerve block (SNB), in children with cerebral palsy (CP). Methods: The current randomized comparative study was conducted on 30 patients with spastic CP aged 2-12 years who were scheduled for unilateral lower limb multilevel soft tissue corrective surgeries, randomly distributed using a computerized program into 2 equal groups. The CEB group received a US-guided caudal block, and the SNB group received a US subgluteal sciatic nerve block. The time to the first postoperative analgesia requirement (primary outcome), postoperative pain score, total postoperative analgesic consumption, and perioperative complications (secondary outcomes) were assessed in both groups. Results: The duration of postoperative analgesia was significantly longer in patients of the SNB (14.65 ± 3.08 h) than in the CEB group (5.93 ± 1.68 h). The postoperative pain scores recorded at 6th-12th h and the postoperative 24-h rescue analgesic consumption were significantly lower in the SNB compared to the CEB group. Conclusions: Ultrasound-guided subgluteal sciatic nerve block is a safe and effective alternative to US-guided caudal analgesia in pediatric patients with spastic CP scheduled for lower limb surgeries, with longer postoperative analgesia and similar perioperative safety profiles.