BACKGROUND Mediastinitis after open-heart surgery is a serious complication that has a decreasing incidence but still a significantly high mortality rate. Back pain may develop during the course of treatment for mediastinitis, and this should suggest vertebral osteomyelitis in the differential diagnosis. Diagnosis of vertebral osteomyelitis may be difficult because of the insidious onset and delayed diagnosis, and treatment may result in serious neurologic compromise and even death of the patient. METHODS This retrospective study involves 5 patients who had open-heart surgery and mediastinitis that was further complicated by vertebral osteomyelitis. Average delay in diagnosis was 18 days after the onset of symptoms. Magnetic resonance imaging was the most helpful tool for diagnosis. Methicilline-resistant Staphylococcus aureus was identified as the responsible microorganism in all patients. Neurologic compromise occured (one paraplegia and one paraparesia) in 2 patients during medical treatment. RESULTS Along with the medical treatment, all patients were surgically treated due to either one or more of the following reasons: unresolving symptoms, sudden neurologic compromise, or impaired spinal column stability despite appropriate conservative treatment. One patient died 10 days postoperatively. The mean follow-up period for the remaining 4 patients was 47 (12 to 95) months. Complete recovery was achieved, and they were able to return to their routine daily activities. CONCLUSIONS Vertebral osteomyelitis should be borne in mind when a patient develops back pain during the course of mediastinitis. Suspicion, early diagnosis with appropriate imaging, and proper treatment are crucial to prevent catastrophic complications.