Background and Objective: Pyogenic spinal infections are rare and potentially devastating, requiring prompt recognition and management. Parallel to the ever-increasing number of invasive spinal procedures, its incidence is on a steady rise, particularly in an expanding elderly population. The aim of this study was to evaluate the efficacy of hyperbaric oxygen (HBO2) therapy in the treatment of this heterogeneous group of disorders. Materials and Methods: Nineteen patients who were referred to our center for HBO2 with a clinical diagnosis of spinal infections (vertebral osteomyelitis, pyogenic spondylitis, spondylodiscitis, surgical site infection following spine surgery, epidural abscess) were retrospectively reviewed. Results: Infection resolution was adequately achieved in 12 of 13 patients (92.3%) on magnetic resonance imaging at the end of HBO2 treatment or during the first month of follow-up. The mean follow-up period was 11 months (range 1 month to 3 years). Conclusions: This study suggests that HBO2 therapy is efficacious in patients with pyogenic spinal infections complicated by primary therapy failure or by medical comorbidities that may impede the eradication of microbial infection and delay wound healing. HBO2 therapy may be useful for reducing long hospital stays, repeated surgeries, and morbidities.