PURPOSE: To evaluate use of positron emission tomography (PEt) with 2 (fluorine-18) fluoro-2-deoxy D-glucose (FDG) in detection of chronic osteomyelitis. MATERIALS AND METHODS: Thirty-one patients suspected to have chronic osteomyelitis in the peripheral (n = 21) or central (n = 10) skeleton were evaluated prospectively with FDG PET. Analysis of the receiver operating characteristic curve was performed. The final diagnosis was made by means of bacteriologic culture of surgical specimens and histopathologic analysis. RESULTS: FDG PET allowed identification of 17 of 18 patients with osteomyelitis and 12 of 13 without osteomyelitis. There was one false- positive and one equivocal result. The area under the ROC curve was 0.96 for all patients, 1.00 for patients suspected to have osteomyelitis in the peripheral skeleton, and 0.88 for patients suspected to have osteomyelitis in the central skeleton. The overall accuracy of FDG PET was 97% with a high degree of interobserver concordance (κ = 0.93). The overall sensitivity and specificity were 100% and 92%, respectively. CONCLUSION: FDG PET enables noninvasive detection and demonstration of the extent of chronic osteomyelitis was a high degree of accuracy. Especially in the central skeleton within active bone marrow, FDG PET is highly accurate and shows great promise in diagnosis of chronic osteomyelitis.