Background: Adjacent segment disease (ASD) is a common complication after lumbar fusion and is still traditionally treated by open surgery. In recent years, with the development of minimally invasive techniques, percutaneous endoscopic surgery(PES) has been used for the treatment of ASD after lumbar fusion due to its unique benefits. Nevertheless, it remains unclear about its significant clinical efficacy and advantages over conventional open surgery., Objectives: To evaluate the clinical efficacy and safety of PES in the treatment of ASD after lumbar fusion., Study Design: A systematic review and meta-analysis studies about the role of PES in managing ASD after lumbar fusion., Methods: A systematic search review was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, WanFang, and SinoMed databases from the start of their construction to 15 November 2021. Eligible studies included references to clinical trials of PES for ASD after open lumbar fusion. Observations included pain relief, recovery of postoperative function, overall excellent rates, and indicators of the advantages of minimally invasive surgery compared to conventional surgery. Postoperative complications and recurrence rates were also recorded., Results: A total of 24 studies, including 20 single-arm studies and 4 clinical control studies, all involving 928 patients were included. A total of 694 patients were included in the single-arm analysis. The results of the single-arm meta-analysis showed that PES could significantly reduce low back and leg pain and improve the functional status of the lumbar spine in patients with ASD after open lumbar fusion compared to preoperatively, and had good clinical efficacy after surgery. A total of 234 patients were included in the four clinically controlled studies, and the results of the meta-analysis showed that PES could clearly reduce pain and improve lumbar function, with no significant difference in efficacy between PES and open surgery. However, PES has a lower surgical incision, less intraoperative bleeding, and shorter operative time and length of hospital stay compared to open surgery. Moreover, it has a lower rate of postoperative recurrence as well as complications and a longer duration of efficacy., Conclusions: On the basis of the available clinical literature and the results of this study, PES could achieve satisfactory clinical effects in ASD treatment after lumbar fusion. Compared with conventional open surgery, PES can not only obtain similar clinical results, but also had the advantages of less trauma and faster recovery. Nevertheless, a randomized controlled study is still needed to validate the findings of this study., Trial Registration: Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022298387., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)