Abstract: [Objective] To compare the clinical efficacy of unilateral and bilateral decompression under unilateral biportal endoscopy (UBE) in moderate to severe lumbar spinal stenosis (LSS) with unilateral symptoms. [Methods] The data of 120 patients with moderate to severe LSS with unilateral symptoms treated with UBE technology from March 2020 to February 2021 were retrospectively analyzed. They were divided into unilateral group (60 cases) and bilateral group (60 cases) according to doctor-patient communication. The data of perioperative period, follow-up and radiographs between the two groups are well analyzed.[Results] All patients were operated smoothly without serious complications. The operation time of unilateral group was shorter than that of bilateral group (P < 0.05); There was no significant difference in other perioperative indicators between the two groups (P > 0.05). Over time, the VAS score and ODI index of the two groups decreased significantly (P < 0.05), while the JOA score increased significantly (P < 0.05). The above scores in the bilateral group were better than those in the unilateral group at 7 days, 3 months after operation and the last follow-up (P < 0.05). In terms of imaging, the dural sac area of the two groups immediately after operation and the last follow-up were significantly higher than that before operation (P < 0.05), but the bilateral group was better than the unilateral group (P < 0.05). There were no significant changes in intervertebral space height and lumbar lordosis angle between the two groups at the immediate after operation and last follow-up (P > 0.05), and there was no statistical difference between the two groups at each time point (P > 0.05). [Conclusion] In the treatment of moderate and severe LSS with unilateral symptoms with UBE technology, the dural sac area of bilateral decompression group increased more than that in the unilateral group, and the operation time was longer than that in the unilateral group, but the clinical effect was better than that in the unilateral group.