Objective To analyze the safety and clinical effect of postemlateral endoscopic lumbar interbody fusion (PE-LIF) under local anesthesia in the treatment of lumbar spondylolisthesis. Methods The clinical data of 58 patients with lumbar spondylolisthesis treated with PE-LIF in our department from Jan. 2020 to Jan. 2022 were retrospectively analyzed. The operation time, intraoperative bleeding, hospital stay and complications were recorded. The clinical efficacy was evaluated by Oswestry dysfunction index (ODI) and visual analogue scale (VAS). Lumbar X-ray films were taken before operation, 1 month, 6 months and 1 year after operation, and the height of intervertebral space, lumbar lordosis angle and anterior lordosis angle of the surgical segment were measured. The accuracy of pedicle screw placement was evaluated by lumbar computed tomography (CT) according to the Gertzbein-Robbins pedicle screw position classification standard 1 month after operation. The fusion rate was evaluated by CT 6 months and 1 year after operation. Results The operation time of the 58 patients was 130-190 (160±30) min, the intraoperative bleeding volume was 52-120 (63±15) mL, and the hospital stay was 6-15 (9.3±3.5) d. All the patients were followed up for 13-26 (17.4±2.8) months. The VAS score of patients with low back pain was 7.28±0.93 before operation and 2.22±0.57 one year after operation, the VAS score of patients with lower limb pain was 7.82±1.40 before operation and 2.38±0.63 one year after operation, the ODI was (65.80±9.88)% before operation and (12.54±4.53)% one year after operation, the height of intervertebral space was (8.3±1.5) mm before operation and (10.8±1.6) mm one year after operation, the lumbar lordosis angle was 31.7°±7.3° before operation and 37.9°±4.4° one year after operation, and the anterior convex angle of the surgical segment was 13.1°±8.1° before operation and 16.1°±2.4° one year after operation, with significant differences in the above indexes (all P＜0.05). One month after surgery, the overall excellent and good rate of pedicle screw placement was 86.64% (201/232). One year after operation, all cases obtained bony fusion without serious complications such as nerve root injury, spinal infection, intraspinal hematoma, fusion cage displacement, or broken nails and rods. Conclusion PE-LIF under local anesthesia is safe and reliable in the treatment of lumbar spondylolisthesis.