We report a retrospective study of 253 patients with vertebral osteomyelitis (VO) who had long-term follow-up. Eleven percent of the patients died, residual disability occurred in more than one-third of the survivors, and relapse occurred in 14%. Median duration of follow-up was 6.5 years (range, 2 days to 38 years). Independent risk factors for adverse outcome (death or qualified recovery) were neurologic compromise, time to diagnosis, and hospital acquisition of infection (P< or =.004). Surgical treatment resulted in recovery or improvement in 86 (79%) of 109 patients. Magnetic resonance images (110 patients) were often obtained late in the course of infection and did not significantly affect outcome. Often, relapse developed in individuals with severe vertebral destruction and abscesses, appearing some time after surgical drainage or debridement. Recurrent bacteremia, paravertebral abscesses, and chronically draining sinuses were independently associated with relapse (P< or =.001). An optimal outcome of VO requires heightened awareness, early diagnosis, prompt identification of pathogens, reversal of complications, and prolonged antimicrobial therapy.