Background: Several studies have compared instrumented PLF with other surgical approaches in terms of clinical outcomes, however little is known about the postoperative HRQoL of patients, especially as regards to degenerative spondylolisthesis.Methods: A group of 62 patients, 30 women (48,4%) and 32 men (51,6%) with mean age 56,73 (SD +/- 9,58) years old, were selected to participate in a 2-year follow-up. Their pain was assessed the visual analogue scale (VAS) for low back pain (VASBP) and leg pain (VASLP) separately. Their HRQoL was evaluated by the Short Form (36) Health Survey (SF-36). Both scales, VAS and SF36, were measured and re-assessed at 10 days, 1 month, 3 months, 6 months, 12 months and 2 years.Results: VASBP, VASLP and each parameter of SF36 presented statistically significant improvement (p<0.01). VASBP, VASLP and SF36 scores did not differ significantly between men and women (p≥0.05). The most notable amelioration of VASBP, VASLP was observed within the first 10 days and the maximum improvement within the first 3 months. From that point, a stabilization of the parameters was observed. The majority of SF36 parameters, and especially PF (physical functioning) and BP (bodily pain), presented statistically significant improvement within the follow up depicting a very similar improvement pattern to that of VAS.Conclusion: We conclude that instrumented PLF ameliorates impressively the HRQoL of patients with degenerative spondylolisthesis after 2 years of follow-up, with pain recession being the most crucial factor responsible for this improvement.