OBJECTIVE Clinical results for unilateral pedicle screw fixation after lumbar interbody fusion have been reported to be as good as those for bilateral instrumentation. However, no studies have directly compared unilateral and bilateral percutaneous pedicle screw fixation after minimally invasive surgery (MIS) for transforaminal lumbar interbody fusion (TLIF). The purpose of this study was to determine whether unilateral percutaneous pedicle screw fixation is comparable with bilateral percutaneous pedicle screw fixation in 1-segment MIS TLIF. METHODS This was a prospective randomized study of 53 patients who underwent unilateral or bilateral percutaneous pedicle screw fixation after MIS TLIF for 1-segment lumbar degenerative disc disease. Twenty-six patients were assigned to a unilateral percutaneous pedicle screw fixation group and 27 patients were assigned to a bilateral percutaneous pedicle screw fixation group. Operative time, blood loss, clinical outcomes (that is, Oswestry Disability Index [ODI] and visual analog scale [VAS] scores), complication rates, and fusion rates were assessed using CT scanning 2 years after surgical treatment. RESULTS The 2 groups were similar in age, sex, preoperative diagnosis, and operated level, and they did not differ significantly in the length of follow-up (27.5 [Group 1] vs 28.9 [Group 2] months) or clinical results. Both groups showed substantial improvements in VAS and ODI scores 2 years after surgical treatment. The groups differed significantly in operative time (unilateral 84.2 minutes; bilateral 137.6 minutes), blood loss (unilateral 92.7 ml; bilateral, 232.0 ml), fusion rate (unilateral 84.6%; bilateral 96.3%), and postoperative scoliotic change (unilateral 23.1%; bilateral 3.7%). CONCLUSIONS Unilateral and bilateral screw fixation after MIS TLIF produced similar clinical results. Although perioperative results were better with unilateral screw fixation, the long-term results were better with bilateral screw fixation, suggesting bilateral screw fixation is a better choice after MIS TLIF.