Abstract:[Objective] To compare the clinical efficacy of unilateral and bilateral decompression under unilateral biportal endoscopy (UBE) for moderate and severe lumbar spinal stenosis (LSS) with unilateral symptoms. [Methods] A retrospective study was conducted on 120 patients who received decompression by UBE for moderate and severe LSS in our department from March 2020 to February 2021. Ac- cording to preoperative doctor- patient communication, 60 patients underwent unilateral decompression, while the remaining 60 patients had bilateral decompression performed. The data regarding to perioperative period, follow-up and radiographs were compared between the two groups. [Results] All patients were operated on smoothly without serious complications. Although the unilateral group consumed signifi- cantly less operation time than the bilateral group (P<0.05) , there was no significant difference in other perioperative indicators between the two groups (P>0.05) . The VAS and ODI scores decreased significantly (P<0.05) , while the JOA score increased significantly in both groups over time (P<0.05) . The bilateral group proved significantly superior to the unilateral group in terms of abovementioned scores at 7 days, 3 months after operation and the latest follow-up (P<0.05) . Radiographically, the dural sac area significantly increased immediately after operation and at the latest follow-up compared with that preoperatively in both groups (P<0.05) , which in bilateral group was better than the unilateral group (P<0.05) . However, the intervertebral space height and local lumbar lordosis angle remained unchanged in both groups postoperatively by comparison with those preoperatively (P>0.05) , which were not statistically significant between the two groups at matching time points (P>0.05) . [Conclusion] Both unilateral and bilateral decompression by using UBE do effectively treat moderate and severe LSS with unilateral symptoms. By contrast, the bilateral decompression does more effectively expand the dural sac area with better clinical outcomes over the unilateral decompression.