OBJECTIVE To analyze the clinical, microbiological, and radiologic features of patients without drug addiction suffering from spontaneous pyogenic vertebral osteomyelitis. METHODS We collected all microbiologically proved cases of pyogenic vertebral osteomyelitis seen between January 1980 and December 1999 in a teaching hospital. Patients with prior spinal instrumentation or surgery and injection drug users were excluded. RESULTS Sixty-four patients, with a mean age of 59 +/- 17 years, were identified. In 29 (45%) patients, 1 or more underlying medical illnesses were found. The mean duration of symptoms before hospital admission was 48 +/- 40 days. Neurologic impairment was present in 18 (28%) patients. Staphylococcus aureus and gram-negative bacilli, mainly Escherichia coli, were the predominant etiologic agents. Blood cultures were positive in 72% (46/64) of cases. The cultures of spinal specimens obtained by x-ray-guided biopsy were positive in 52% (11/21) of cases, and those obtained by open biopsy in 75% (15/20) of cases. Plain radiography showed abnormalities in all but 7 patients. Fifty-one of 53 (96%) technetium Tc 99m diphosphonate bone scans and 40 of 44 (91%) gallium citrate Ga 67 bone scans showed increased uptake of tracers in the involved area. Paraspinal and epidural extension was found on computed tomography and/or magnetic resonance imaging in 74% (39/53) of cases; the presence of an extra-vertebral extension was not associated with the development of neurologic findings in many patients. Two patients died in relation to the infectious process and 3 relapsed; functional sequelae often were found. CONCLUSIONS Spontaneous pyogenic vertebral osteomyelitis in nondrug users is a disease that affects mainly older patients suffering underlying medical illnesses. S aureus and E coli are the main causative microorganisms. Positive blood cultures frequently aided the diagnosis. Extra-vertebral extension is frequent but does not indicate a worse prognosis. Although life outcome is good, functional sequelae are common. Diagnostic delay before admission is a concern, and the physician should be alert to the possibility of this condition in patients with back or neck pain.