This was a retrospective study. We aimed to compare the clinical efficacy and safety between minimally invasive and traditional open transforaminal lumbar interbody fusion in the treatment of low-grade lumbar degenerative spondylolisthesis (LDS). 81 patients with LDS grades 1 and 2 treated in our spinal department from January 2014 to July 2016 were retrospectively analyzed. The MIS-TLIF group included 23 males and 11 females, while the TO-TLIF group included 29 males and 18 females. Follow-up points were set at 7 days, 3 months, 6 months, 12 months postoperatively and the last follow-up. Various clinical and radiological indicators were used to evaluate and compare the efficacy and safety between the two procedures. 8 cases (3 in the MIS-TLIF group and 5 in the TO-TLIF group) were loss of follow-up after discharge. And the remaining 73 patients were followed up for at least 2 years. No statistically significant difference was observed in the terms of age, sex, BMI, slippage grade, and surgical segments. The MIS-TLIF group had a longer operation and fluoroscopy time compared with the TO-TLIF group. But the MIS-TLIF group was associated with less blood loss, ambulation time, hospital stay, and time of return to work. In each group, significant improvement were observed in BP-VAS, ODI and vertebral slip ratio at any time-point of follow-up when compared with the preoperative condition. When the time-point of follow-up was less than 1 year, the MIS-TLIF group had significant advantages in the BP-VAS and ODI compared with TO-TLIF group. But no significant difference was observed in the BP-VAS and ODI at either 12 month follow-up or the last follow-up. Besides, no statistical difference was detected in vertebral slip ratio at any time-point of follow-up between the two groups. Successful intervertebral bone fusion was found in all patients and no significant difference was found in the incidence of total complications. Thus, we considered that MIS-TLIF and TO-TLIF both achieve satisfactory clinical efficacy in the treatment of low-grade single-segment LDS. But MIS-TLIF appears to be a more efficacious and safe technique with reduced tissue damage, less blood loss and quicker recovery.