Our aim was to evaluate the role of SPECT/CT for the diagnosis of diabetic foot infection by labeled leukocytes. Methods: Seventeen patients with 19 clinically suspected sites of infection were included. After leukocyte labeling and administration, planar scans were acquired at 30 min, 4 h, and 24 h for 18 consecutive patients. SPECT/CT was obtained at 6 h. The final diagnosis was established by clinical follow-up (24 mo) in all cases and by bone biopsy for 14 sites. Results: Leukocyte scanning was positive in 16 of 19 lesions and negative in 3. SPECT/CT changed the interpretation of the planar and SPECT images for 10 of 19 suspected sites (52.6%): it excluded osteomyelitis in 6 cases, revealed bone infection in 1 case, and revealed both bone and soft-tissue infection in 3 cases. The hybrid device did not significantly contribute to the evaluation of patients with negative scan results. Conclusion: SPECT/CT can be useful for a more accurate diagnosis of diabetic foot infection by labeled leukocyte imaging. Copyright © 2009 by the Society of Nuclear Medicine, Inc.