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Abstract Background Pyogenic vertebral osteomyelitis (PVO), which is a potentially life-threatening condition and is associated with significant morbidity and mortality, is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study is to compare the efficacy of posterior single-segment and short-segment fixation combined with one-stage posterior debridement and fusion for the treatment of mono-segmental lumbar or lumbosacral PVO. Methods Charts of all patients with mono-segmental lumbar or lumbosacral PVO were treated by single-stage posterior debridement, bone graft fusion, and pedicle screw fixation from April 2012 to January 2016. All patients were divided into two groups: sinlge-segment fixation (Group A, n = 31) and short-segment fixation (Group B, n = 36). These patients were followed up for a minimum of five years. The clinical efficacy was evaluated and compared on average operation time, blood loss, visual analog scale (VAS), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), neurological function recovery and local lordotic angle. Results All 67 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and pain relief at the final follow-up. The VAS was 7.1 ± 0.7 in group A and 7.2 ± 0.6 in group B pre-operatively, which decreased to 2.1 ± 0.6 and 2.0 ± 0.7, respectively, at three months after surgery, then reduced to 0.4 ± 0.5 and 0.5 ± 0.5, respectively, at the final follow-up. ESR, CRP returned to normal limits in all patients 3 months after surgery. The mean blood loss and operation time in group A were less than that in group B (P |