Objective To compare the mid-term effectiveness of unilateral biportal endoscopy (UBE)-transforaminal lumbar interbody fusion (TLIF) and minimally invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) assisted with three-dimensional microscope in the treatment of single-level lumbar spondylolisthesis. Methods A total of 41 single level lumbar spondylolisthesis patients who met the selection criteria were retrospectively collected between June 2018 and September 2019. Twenty-three patients were treated with UBE-TLIF (study group) and 18 with MIS-TLIF assisted with three-dimensional microscope (control group). There was no significant difference in gender, age, Meyerding degree of slippage, type of spondylolisthesis, lesion segment, course of disease, and preoperative hemoglobin (Hb) level, visual analogue scale (VAS) score, Oswestry disability index (ODI), lumbar lordosis (LL), and disc height (DH) between the two groups (P>0.05). The operation time, hospitalization time, intraoperative blood loss, Hb level between preoperative and postoperative at 1 day, and complications were compared between the two groups. The recovery of clinical sign and symptom was evaluated by VAS score and ODI before operation, and at 1 month, 3 months, 1 year, and 3 years after operation. The LL and DH were measured by radiography before operation and at last follow-up, and the fusion rate was calculated according to Suk grade at last follow-up. ResultsAll the operations were successfully completed. There was no significant difference in operation time between the two groups (P>0.05); the hospitalization time, intraoperative blood loss, and Hb difference between pre- and post-operation in the study group were significantly less than those in the control group (P<0.05). Both groups were followed up 36-48 months, with an average of 39.2 months. In the study group, 1 case of dural tear and 2 cases of Cage subsidence occurred, without postoperative infection and epidural hematoma; in the control group, infection occurred in 1 case, dural tear in 2 cases, Cage subsidence in 1 case, and no epidural hematoma occurred; there was no significant difference in the incidence of complications between the two groups (13.04% vs. 22.22%) (χ2=0.601, P=0.438). The VAS score and ODI at each time point after operation in both groups significantly improved when compared with those before operation, and further improved with time (P<0.05). There was no significant difference in VAS scores between the two groups at each time point after operation (P>0.05); the ODI of the study group was significantly lower than that of the control group at 1 and 3 months after operation (P<0.05), and there was no significant difference between the two groups at other time points (P>0.05). The imaging test showed that the intervertebral fusion rates were 95.7% in the study group and 94.4% in the control group at last follow-up, with no significant difference (χ2=0.032, P=0.859). At last follow-up, LL and DH in the two groups significantly improved when compared with those before operation (P<0.05), and the difference between before and after operation showed no significant difference between the two groups (P>0.05). ConclusionBoth UBE-TLIF and MIS-TLIF assisted with three-dimensional microscope have the advantages of clear intraoperative field and high surgical efficiency in treating lumbar spondylolisthesis, and can obtain satisfactory mid-term effectiveness. Compared with MIS-TLIF assisted with three-dimensional microscope, UBE-TLIF has the advantages of less bleeding and faster recovery.