Study Design Retrospective cohort study. Objective To evaluate whether the proposed one-stage biopsy, culture, debridement, and reconstruction with stabilization strategy is a viable option for pyogenic vertebral osteomyelitis (PVO). PVO is increasing in frequency globally, particularly in immunologically compromised individuals. Typically, biopsy and culture sensitivity followed by staged surgery and long-term antibiotic therapy is the mainstay of therapy. Methods This is a study of a group of 32 consecutive cases of PVO (spondylodiskitis) treated in our institution from 2010 to 2012. All cases had one-stage biopsy, culture sensitivity, debridement, reconstruction with iliac bone graft, and stabilization with titanium implants. The mean age in this series was 51 years, and the male-to-female ratio was 2.2:1. Approximately 50% of the patients had impaired immunity status. The commonest organism isolated was Pseudomonas aeruginosa. Culture-specific antibiotics were given for a minimum of 6 weeks to all patients. The follow-up period ranged from 6 months to a maximum of 2 years. All patients were assessed for wound healing, recurrence of infection, deformity progression, pain, and healing by radiologic and biochemical parameters. No generic or disease-specific outcome tools were used for this study. Results All patients had good wound healing, although there was one case of superficial infection that was resolved with debridement. There were two implant failures with pseudarthrosis and one localized kyphosis in this series. Conclusions The one-stage technique of biopsy, debridement, bone grafting, and stabilization can be recommended for most cases of PVO.