Effective pain management is crucial in cleft lip and palate (CLP) patients undergoing orthognathic surgery for earlier recovery and decreased opioid reliance. Liposomal bupivacaine (Exparel) is a local anesthetic that provides extended postoperative analgesia in adult patients; however, research on its use in adolescents is limited. This study explores the efficacy of liposomal bupivacaine for postoperative pain management in adolescent CLP patients undergoing orthognathic surgery. The authors performed a retrospective chart review at their institution between July 2020 and December 2022 to identify patients who underwent LeFort I or mandibular osteotomy. Two cohorts were compared: patients who received liposomal bupivacaine and patients who received standard pain medications alone. Outcome measures included intraoperative pain medications, length of stay, breakthrough opioid use, time to first oral intake, volume of oral intake, and opioids prescribed at discharge. This study included 22 patients who underwent orthognathic surgery. The liposomal bupivacaine group (n=10) demonstrated earlier and greater oral intake during hospitalization compared with controls (n=12). The most significant difference was observed in total breakthrough opioid use, with an average of 8.60 morphine milligram equivalents for liposomal bupivacaine patients compared with 35.1 morphine milligram equivalents for controls (P=0.037). This study provides the first analysis of liposomal bupivacaine use in adolescent CLP patients undergoing orthognathic surgery, demonstrating a significant reduction in postoperative opioid consumption compared with controls. These results may guide future studies of liposomal bupivacaine within CLP patients, potentially as a component of enhanced recovery after surgery guidelines, as well as in cost-analysis studies.