The X-Stop interspinous distraction device has shown to be an attractive alternative to conventional surgical procedures in the treatment of symptomatic degenerative lumbar spinal stenosis. However, the effectiveness of the X-Stop in symptomatic degenerative lumbar spinal stenosis caused by degenerative spondylolisthesis is not known. A cohort of 12 consecutive patients with symptomatic lumbar spinal stenosis caused by degenerative spondylolisthesis were treated with the X-Stop interspinous distraction device. All patients had low back pain, neurogenic claudication and radiculopathy. Pre-operative radiographs revealed an average slip of 19.6%. MRI of the lumbosacral spine showed a severe stenosis. In ten patients, the X-Stop was placed at the L4-5 level, whereas two patients were treated at both, L3-4 and L4-5 level. The mean follow-up was 30.3 months. In eight patients a complete relief of symptoms was observed post-operatively, whereas the remaining 4 patients experienced no relief of symptoms. Recurrence of pain, neurogenic claudication, and worsening of neurological symptoms was observed in three patients within 24 months. Post-operative radiographs and MRI did not show any changes in the percentage of slip or spinal dimensions. Finally, secondary surgical treatment by decompression with posterolateral fusion was performed in seven patients (58%) within 24 months. In conclusion, the X-Stop interspinous distraction device showed an extremely high failure rate, defined as surgical re-intervention, after short term follow-up in patients with spinal stenosis caused by degenerative spondylolisthesis. We do not recommend the X-Stop for the treatment of spinal stenosis complicating degenerative spondylolisthesis.