Degenerative spondylolisthesis is characterized by the slippage of one vertebral body over the one below, with association of intervertebral disc degeneration and degenerative arthritis of the facet joints, which cause spinal stenosis. The aim of this study was to evaluate the clinical and radiographic results of 22 patients with symptomatic degenerative spondylolisthesis, operated on by decompressive laminectomy and instrumented posterolateral fusion associated with interbody fusion (PLIF). Mean age at surgery was 64 years (range, 57–72). Clinical results were evaluated on a questionnaire at the last follow-up visit concerning postoperative low back and leg pain, restriction of daily life activities, and resumption of sports activity. Lumbar spine radiographs were used to evaluate the status of fixation devices, the reduction of the spondylolisthesis, the lumbar sagittal balance and the presence of spinal fusion. No intraoperative or postoperative complications were encountered. There were no superficial or deep infections, fixation device loosening, or hardware removal. Mean follow-up time was 4 years (range, 3–6 years). Clinical outcome was excellent or good in 19 patients and fair in 3 patients. Preoperatively, mean forward vertebral slipping on neutral lateral radiographs was 5 mm, while postoperatively it decreased to 3 mm. Preoperatively, mean sagittal motion was 3 mm and angular motion was 8°, while postoperatively these values decreased to 1 mm and 1°, respectively. This study demonstrated that spinal decompression followed by transpedicular instrumentation associated with PLIF technique is a valid surgical option for the treatment of degenerative spondylolisthesis with symptomatic spinal stenosis. Clinical outcome, intended as relief of pain and resumption of activity, was improved significantly and fusion rate was high.