Study Design: A retrospective case-control study. Objective: To compare the clinical efficacy of endoscopic (Endo) and open posterior lumbar interbody fusion (PLIF) in treating lumbar spondylolisthesis. Background: Endo-PLIF has emerged as a new technique for treating lumbar spondylolisthesis. We propose Endo-PLIF as an alternative method. Materials and Methods: Sixty-four patients with single-segment lumbar spondylolisthesis underwent Endo-PLIF (n = 39) or open PLIF (n = 25) treatment. Demographic data, perioperative parameters, and radiographic parameters were recorded. Clinical results were evaluated by Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores. The fusion rate was evaluated by computed tomography at 12 months postoperatively. In addition, a case-control process was included to ensure unbiased comparisons. Results: The average operation time was longer in the Endo-PLIF group. Endo-PLIF showed advantages in reducing blood loss, shortening hospital stay, and early ambulation, but with a longer x-ray exposure time. Both VAS and ODI scores significantly improved in both groups, but the VAS for back pain was lower in the Endo-PLIF group. The radiographic results were similar in both groups. Three patients in the Endo-PLIF group had minor complications. Two patients in the open PLIF group experienced cerebrospinal fluid leakage. Both VAS and ODI scores significantly improved in both groups compared with preoperative scores, but the Endo-PLIF group showed more significant improvement at early follow-up (P < 0.05). There was no significant difference in interbody fusion rate between the two groups. Conclusion: Both Endo-PLIF and open PLIF are effective for treating single-segment lumbar spondylolisthesis. Endo-PLIF shows advantages in reducing blood loss, shortening hospital stays, and promoting early ambulation, with comparable fusion rates and patient satisfaction to open PLIF. Despite minor complications in the Endo-PLIF group and cerebrospinal fluid leakage in the open PLIF group, both procedures lead to significant improvements in pain and disability scores, with Endo-PLIF demonstrating more significant early improvements.