BACKGROUNDLiposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.OBJECTIVESTo compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.DESIGNA systematic review and meta-analysis with trial sequential analysis.DATA SOURCESMEDLINE, Embase and Web of Science, among others, up to June 2022.ELIGIBILITY CRITERIAWe retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.RESULTSTwenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h (P = 0.15), 48 h (P = 0.15) and 72 h (P = 0.07). The quality of evidence was moderate.CONCLUSIONSThere is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.