Objective To compare the efficacy and safety of percutaneous endoscopic interlaminar discectomy by the lateral decubitus position (LDP) and prone position (PP) in treatment of simple L₅/S₁ disc herniation (LDH).Methods Clinical data of 51 patients with simple L₅/S₁ LDH underwent percutaneous endoscopic interlaminar discectomy from January 2017 to January 2018 were retrospectively analyzed. They were divided into LDP group and PP group according to different intraoperative position. LDP group (n = 20) had 12 males and 8 females, the average age was (54.33 ± 9.13) years from 33 to 78 years; PP group (n = 31) had 18 males and 13 females, the average age was (52.31 ± 6.54) years from 30 to 68 years. The operative time, the times of intraoperative fluoroscopy, the discomfort caused by body position and the incidence of neck pain were recorded. The intraoperative discomfort was evaluated by Likert score, and the VAS and ODI scores of lumbar and legs pain before and after the operation were compared between the two groups. Finally, the efficacy of the last follow-up was evaluated according to the modified MacNab.Results In LDP group, the operation time was 40 ~ 100 min, with an average of (61.59 ± 14.27) min, the average number of fluoroscopy was 2 ~ 6 times, with an average of (3.32 ± 0.22) times, and the Likert score was (3.93 ± 0.73), only one patient had mild neck pain during the whole operation. In the PP group, the operation time was 45 ~ 90 min, with an average of (60.38 ± 15.42) min, the number of fluoroscopy was 2~4 times, with an average of (3.23 ± 0.14) times, the Likert score was (3.49 ± 0.65), 5 patients suffered neck pain. There were no significant difference in the time of operation and the times of fluoroscopy between the two groups (P > 0.05). The VAS and ODI scores of the two groups after surgery were significantly different from those before surgery (P < 0.05); There were no significant differences in VAS, ODI scores and last MacNAB scores between the two groups (P > 0.05). The Likert score in the LDP group was higher than that in the PP group, and the incidence of neck pain was lower than that in the PP group (P < 0.05). One patient in the PP group developed plantar flexor paralysis, and the muscle strength recovered to level 4 after conservative treatment. There were no complications such as cerebrospinal fluid leakage, segmental errors, and intervertebral space infection.Conclusion Both LDP and PP percutaneous endoscopic interlaminar discectomy in treatment of simple L₅/S₁ LDH, but the former has high comfort and easier to cooperate and be accepted, it can be popularized and applied in clinic.