ObjectiveThis meta‐analysis aimed to determine whether liposomal bupivacaine (LB) single‐injection could achieve an analgesic effect similar to that of continuous local anesthetic nerve blocks (CNBs) after painful surgeries.MethodsEmbase, PubMed, and the Cochrane Library databases were comprehensively searched. Randomized controlled trials (RCTs) with a modified Jadad score ≥ 4 compared LB single‐injection with CNBs in patients after painful surgeries were included. The primary outcomes were VAS pain score and opioid consumption. The secondary outcomes were complications and length of hospital stay. Review Manager 5.3 and trial sequential analysis (TSA) 0.9.5.10 were used to analyze the extracted data.ResultsSix RCTs of 625 patients were included for meta‐analysis. Both groups in 5 RCTs described standard concomitant treatment with multimodal analgesia. There were no significant differences in mean VAS scores for postoperative day 0 (P = 0.12), day 1 (P = 0.18), and day 2 (P = 0.41); highest VAS scores for day 0 (P = 0.18), day 1 (P = 0.46), and day 2 (P = 0.18); total opioid consumption for day 0 (P = 0.05), day 1 (P = 0.28), and day 2 (P = 0.57); complications (P = 0.30); and length of hospital stay (P = 0.64) between the 2 groups. TSA of primary outcomes showed that all cumulative Z curves failed to cross the TSA boundary and did not reach the required information size.ConclusionsThis meta‐analysis showed that LB single‐injection and CNBs have similar efficacy of pain relief and safety in patients after painful surgeries when concomitant with multimodal analgesia. However, the results of TSA indicate that further trials are still needed to confirm these findings.