Summary. Pyogenic spondylodiscitis is an uncommon but severe spinal infection. In majority of cases treatment is based on intravenous antibiotics and rigid brace immobilization. Posterior percutaneous spinal instrumentation is a safe alternative procedure in relieving pain, preventing deformity and neurological compromise. Introduction. Pyogenic spondylodiscitis (PS) is an uncommon but severe spinal infection. Patients affected by a non-complicated PS and treatment is based on intravenous antibiotics and rigid brace immobilization with a thoracolumbosacral orthosis (TLSO) suffices in most cases in relieving pain, preventing deformity and neurological compromise. Since January 2010 we started offering patients percutaneous posterior screw-rod instrumentation as alternative approach to TLSO immobilization. The aim of this study was to evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single level lower thoracic (T9-T12) or lumbar pyogenic spondylodiscitis. Materials and Methods. Retrospective cohort analysis on 27 patients diagnosed with PS who were offered to choose between 24/7 TLSO rigid bracing for 3 to 4 months and posterior percutaneous screw-rod instrumentation bridging the infection level followed by soft bracing for 4 weeks after surgery. All patients underwent antibiotic therapy. Fifteen patients chose conservative treatment, 12 patients chose surgical treatment. Patients were seen at 1, 3, 6, 9 months after diagnosis. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and complete blood count were measured at each follow-up visit. Segmental kyphosis was measured at diagnosis and at 9 months. VAS, SF-12, and EQ-5D questionnaires were recorded at each follow-up visit. Baseline groups’ demographic characteristics were assessed using independent sample t-tests for continuous variables and χ2 tests for frequency variables. Results. Complete healing was achieved in all patients, no difference was observed in healing time between the two groups (77.3±7.2 days vs 80.2±4.4). Instrumentation failure and screw loosening was not observed in any patient. In both group CRP and ESR decreased accordingly with response to antibiotic therapy. Surgically treated patients had significantly lower VAS scores at 1 month (3.05±0.57 in surgery group vs 5.20±1.21 in TLSO group) and 3 months (2.31±0.54 in surgery group vs 2.85±0.55 in TLSO group) post-diagnosis. Both groups had similar trends toward fast recovery in both mental (MCS) and physical components (PCS) of SF-12 questionnaire, surgically treated patients showed steeper and statistically significative improvement at 1 month (37.83±4.57 MCS in surgery group vs 24.52±3.03 MCS in TLSO group and 35.46±4.43 PCS in surgery group vs 27.07±4.45 PCS in TLSO group, p<0.001), 3 months (52.94±3.82 MCS in surgery group vs 39.45±4.92 MCS in TLSO group and 44.93±3.73 PCS in surgery group vs 35.33±6.44 PCS in TLSO group, p<0.001), and 6 months (54.93±3.56 MCS in surgery group vs 49.99±5.82 MCS in TLSO group) post-diagnosis, no statistically significant differences were detected at the other time points (9 months post-diagnosis). EQ-5D index was significantly higher in surgery patients at 1 month (0.764±0.043 in surgery group vs 0.458±0.197 in TLSO group) and 3 months (0.890±0.116 in surgery group vs 0.688±0.142 in TLSO group); no statistically significant changes were observed in segmental kyphosis between the two groups. Conclusion. Posterior percutaneous spinal instrumentation is a safe, feasible, and effective procedure in relieving pain, preventing deformity and neurological compromise. Surgical stabilization was associated with faster recovery, lower pain scores, and improved quality of life compared with TLSO conservative treatment at 1 and 3 months after diagnosis