Objective To compare the effectiveness of posterolateral approach lumbar interbody fusion assisted by one-hole split endoscope (OSE) and traditional posterior lumbar interbody fusion (PLIF) in the treatment of L4, 5 degenerative lumbar spondylolisthesis (DLS). Methods The clinical data of 58 patients with DLS who met the selection criteria admitted between February 2020 and March 2022 were retrospectively analyzed, of which 26 were treated with OSE-assisted posterolateral approach lumbar interbody fusion (OSE group) and 32 were treated with PLIF (PLIF group). There was no significant difference between the two groups in terms of gender, age, body mass index, Meyerding grade, lower limb symptom side, decompression side, stenosis type, and preoperative low back pain visual analogue scale (VAS) score, leg pain VAS score, Oswestry disability index (ODI), and the height of the anterior and posterior margins of the intervertebral space (P>0.05). The operation time, intraoperative blood loss, postoperative hospital stay, and complications were compared between the two groups. The low back pain and leg pain VAS scores and ODI before operation, at 1 month, 6 months after operation, and last follow-up, the height of anterior and posterior margins of the intervertebral space before operation, at 6 months after operation, and last follow-up, the modified MacNab criteria at last follow-up after operation were used to evaluate the effectiveness; and the Bridwell method at last follow-up was used to evaluate the interbody fusion. Results Both groups successfully completed the operation. Compared with the PLIF group, the OSE group showed a decrease in intraoperative blood loss and postoperative hospital stay, but an increase in operation time, with significant differences (P<0.05). In the OSE group, no complication such as nerve root injury and thecal sac tear occurred; in the PLIF group, there were 1 case of thecal sac tear and 1 case of epidural hematoma, which were cured after conservative management. Both groups of patients were followed up 13-20 months with an average of 15.5 months. There was no complication such as loosening, sinking, or displacement of the fusion cage. The low back pain and leg pain VAS scores, ODI, and the height of anterior and posterior margins of the intervertebral space at each time point after operation in both groups were significantly improved when compared with those before operation (P<0.05). Except for the VAS score of lower back pain in the OSE group being significantly better than that in the PLIF group at 1 month after operation (P<0.05), there was no significant difference in all indicators between the two groups at all other time points (P>0.05). At last follow-up, both groups achieved bone fusion, and there was no significant difference in Bridwell interbody fusion and modified MacNab standard evaluation between the two groups (P>0.05). Conclusion OSE-assisted posterolateral approach lumbar interbody fusion for L4, 5 DLS, although the operation time is relatively long, but the postoperative hospitalization stay is short, the complications are few, the operation is safe and effective, and the early effectiveness is satisfactory.