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Background and Aims This systematic review and meta-analysis aims to compare the pain-related and functional outcomes of liposomal bupivacaine (LB) versus plain local anesthetic (LA) for adductor canal block (ACB) in adult patients undergoing knee surgery.

Methods Studies were evaluated in major electronic databases from inception to March 2023, with a search rerun in April 2024. Studies involving additional surgery areas or comparing periarticular infiltrations with ACB were excluded. The study protocol was registered with PROSPERO: CRD42022376835. The primary outcomes were pain scores and opioid consumption in the first 24 hours postoperatively. Secondary outcomes included length of hospital stay (LOHS), pain scores at different time points post-surgery, and associated complications.

Results Ten trials with 2847 patients (LB=1873, plain LA=974) were included. LB was associated with lower pain scores at 24 hours (SMD = -0.27; 95% CI -0.45 to -0.09; p = 0.003), 48 hours (SMD = -0.34; 95% CI -0.42 to -0.28; p <0.00001), and 72 hours (SMD = -0.30; 95% CI -0.45 to -0.15; p=0.0001). Oral morphine equivalent dosage was lower in the LB group at 24 hours (SMD = -0.48; 95% CI -0.92 to -0.03; p = 0.04). There was no significant difference in LOHS between groups (SMD=0.09 hours; 95% CI -0.02 to 0.20; p=0.12). No significant complications were observed. The overall quality of evidence was low to very low for all outcomes.

Conclusions While LB showed statistically significant improvements in pain scores and opioid consumption compared to plain LA, these did not translate to clinically meaningful benefits.