Six patients with osteoporosis had vertebral osteomyelitis (VO) with infection of a single vertebra that presented with a collapsed vertebral body, thought to be a simple compression fracture. The resulting delay in correctly diagnosing VO was associated with disabling sequelae in a high proportion of cases. This distinctive presentation accounted for 13% of all hospitalized patients with VO and 2.4% of inpatients with osteoporotic compression fractures during the last five years; it may be more common than suggested by the paucity of published cases. In patients with osteoporosis and vertebral compression fractures, osteomyelitis should be considered when there is severe back pain, persistent unexplained fever, unexplained elevation of the erythrocyte sedimentation rate, or bacteremia without an obvious extravertebral focus of infection, particularly if the patient is immunocompromised. Early biopsy and culture of the collapsed vertebral body will facilitate diagnosis and therapy.