Background and Objectives: Degenerative spondylolisthesis is frequently associated with LBP and leg pain. When conservative treatment fails to relief symptoms, the surgical spine fixation and neural tissue decompression becomes the treatment of choice as it leads to functional and symptomatic improvement. In this study we compare between percutaneous spine fixations versus open spine fixation in cases of degenerative spondylolisthesis. Patients and Methods: 40 patients with degenerative spondylolisthesis were divided randomly and equally in two groups, group A of patients underwent spine fixation with conventional open surgery approach, while group B underwent percutaneous spine fixation, we recorded intraoperative difficulties and post-operative outcome in the two groups every 6 months for 18 months. Results: The mean operation time was 174 minutes in group A and 168 minutes in group B, the mean amount of blood loss in group A was 443 ml, while was 165 ml in group B (p value < 0.001), the mean duration of hospital stay in group A was 2.45 days, while it was 1.8 day in group B (p value <0.002), there is no statistically significant difference between the two groups in reduction of leg pain, back pain and ODI either immediately post-operative or after 6, 12, and 18 months of follow up Conclusions: Percutaneous spine fixation has the advantage of being less invasive, with less intra operative bleeding, less operation time and post-operative hospital stay than the conventional open spine fixation technique. However, both techniques have the same results of improving patients' leg and back pain on the long term.