Efficacy of Liposomal Bupivacaine in Third Molar Extraction: A Systematic Review and Meta-Analysis

Third molar extraction is a common surgical procedure, and it is associated with significant postoperative pain. Liposomal bupivacaine (LB) is an extended-release local anesthetic. This intervention was developed in its current form to provide prolonged analgesia and reduce opioid use. However, its efficacy in third molar surgery remains inconclusive and inconsistent. In this systematic review and meta-analysis, we aim to evaluate the efficacy of LB in third molar extraction. We systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library up to January 2026 for randomized controlled trials (RCTs) and observational studies comparing LB to standard bupivacaine or placebo. We performed the meta-analysis using R software with a random-effects model. Continuous outcomes were assessed using mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs). Four studies (three RCTs, one observational) with 858 participants were included. LB showed a statistically significant but clinically negligible reduction in opioid consumption at 48 hours (MD -1.20 morphine milligram equivalents (MME); 95% CI -1.79 to -0.61). One study reported a substantial reduction in opioid prescriptions (MD -66.70 MME). For analgesia, there was no statistically significant difference between LB and control in postoperative pain intensity (SMD -0.21; 95% CI -0.51 to 0.10) or cumulative pain scores (SMD -1.06; 95% CI -2.52 to 0.39) over 0-48 hours, with high heterogeneity in the latter (I² = 96.9%). Our findings indicate that while LB was associated with a significant reduction in opioid consumption, the effect size is not clinically meaningful, with a limited difference in postoperative pain. However, the limited number of included studies highlights the need for cautious interpretation, with further large-scale RCTs needed to validate these findings.