Purpose <p>Symptomatic lumbar spondylolisthesis is usually treated with fusion surgery when conservative methods fail. However, traditional open decompression and fusion involves a large skin incision and muscle detachment. Therefore, minimally invasive techniques have been developed to reduce tissue damage, potentially leading to less postoperative pain and earlier resumption of activities. The purpose of this study was to compare percutaneous versus open pedicle screw placement in patients receiving lumbar midline decompression due to symptomatic lumbar spondylolisthesis focusing on short-term low back pain.</p> Methods <p>A randomised controlled trial was conducted in 2 Dutch hospital from 2015 to 2020. Participants with spondylolytic or degenerative lumbar spondylolisthesis were randomised into percutaneous pedicle screw placement with a mini-open decompression (mini-open), or conventional open surgery with instrumented fusion (open). The primary outcome measure was short-term low back pain after 2 weeks, measured by a visual analogue scale. Leg pain, disability and quality of life were recorded at 2 and 6 weeks, 3 and 6 months and 1 year. Surgical variables, including complications, were recorded. Analyses were performed in the intention-to-treat population.</p> Results <p>In total, 169 participants were included and randomised to mini-open (<i>n</i> = 81) or standard open surgery (<i>n</i> = 88). No statistically or clinically significant differences were found between groups in terms of primary or secondary outcomes. Surgery duration, blood loss, hospital stay, and complications were also similar between groups.</p> Conclusions <p>This study detected no difference in outcome between mini-open compared to open surgery in patients with spondylolisthesis. The hypothetical advantage of reduced short-term low back pain, less blood loss and better clinical outcome could not be confirmed.</p>