Unilateral pedicle screw (UPS) fixation has been applied in oblique lumbar interbody fusion (OLIF). However, the internal fixation strength required by OLIF is still controversial. Although satisfactory short-term outcome has been achieved with OLIF combined with UPS, the maintenance of stability in the fused segment remains a concern due to the lack of mid-term to long-term clinical follow-up reports. In this study, we compared the mid-term to long-term radiographic and clinical outcomes of unilateral (n = 100) versus bilateral (n = 86) instrumented one-level OLIF for lumbar degenerative disease (LDD).The mean follow-up duration was 75.09 ± 5.08 months. A significant decrease occurred in operative time, blood loss in UPS group. No statistical difference was detected regarding complication rate and fusion rate between the two groups. The VAS of low back pain at 6 months postoperatively was better than that of the BPS group. However, there were no significant differences in VAS and ODI at any other follow-up time point. The incidence of ASD was 12% lower in the UPS group than the 18.6% observed in the BPS group at the final follow-up. The standardized cross sectional area (SCSA) and degree of fat infiltration (DFF) of the multifidus muscle (MM) were better than those of the BPS group in the same period. The current data show that OLIF-UPS for the treatment of single-level LDD could achieve satisfactory mid-term to long-term outcomes comparable to BPS fixation, with less surgical time, less blood loss, and less DFF of the MM.