PurposeCombination of regional anaesthesia technique that is most effective in analgesia and postoperative functional outcome with the fewest complications needs investigation. Interspace between the popliteal artery and the capsule of the posterior knee block (IPACK) has been introduced clinically. We evaluated the efficacy of IPACK in combination with other nerve blocks after total knee arthroplasty.MethodsData were obtained from PubMed, Cochrane Library, Web of Science, and Sciencedirect. Studies that compared outcomes using IPACK combined with other regional nerve blocks after total knee arthroplasty with other analgesic modalities and those which used pain scores or opioid consumption as primary or secondary outcomes were included.ResultsSeventeen articles (20 trials, 1652 patients) were included. IPACK supplementation significantly reduced rest pain scores after total knee arthroplasty at postoperative hours 8–12(95%CI − 0.85 [− 1.36, − 0.34], I2 = 94%, p = 0.001), postoperative day 1 (95% CI − 0.49 [− 0.85, − 0.14], I2 = 87%, p = 0.006), and postoperative day 2 (95% CI − 0.28 [− 0.51, -0.05], I2 = 72%, p = 0.02); there was no significant difference at postoperative day 3 or discharge (95% CI − 0.14 [− 0.33, 0.05], I2 = 0%, p = 0.14). Combination treatment resulted in reduced dynamic pain scores at postoperative hours 8–12 (95%CI − 0.52 [− 0.92, − 0.12], I2 = 86%, p = 0.01) and postoperative day 1(95% CI − 0.49 [− 0.87, − 0.11], I2 = 88%, p = 0.01). There was no difference between postoperative day 2(95% CI − 0.29 [− 0.63, 0.05], I2 = 80%, p = 0.09), postoperative day 3 or discharge (95% CI − 0.45 [− 0.92, 0.02], I2 = 83%, p = 0.06). In addition, it strongly reduced postoperative opioid consumption within 24 H (95% CI − 0.76 [− 1.13, − 0.39], I2 = 85%, p < 0.00001), 24–48 H (95% CI − 0.43 [− 0.85, − 0.01], I2 = 83%, p = 0.04), and total opioid use (95% CI − 0.64 [− 1.07, − 0.22], I2 = 86%, p = 0.003). Although IPACK supplementation improved timed up and go test and walking distance at postoperative day 2, there was no statistically significant difference at other time periods or obvious improvement in knee range of motion and quadriceps strength. IPACK block supplementation could shorten the length of stay (LOS) (95% CI − 0.40 [− 0.64, − 0.15], I2 = 70%, p = 0.001) and improve patient satisfaction (95% CI 0.43 [0.01, 0.84], I2 = 87%, p = 0.04).ConclusionBased on these results, IPACK supplementation, in addition to standard postoperative analgesia, can be used effectively and safely to relieve early postoperative pain after total knee arthroplasty.