Aim of the study: To evaluate the role of Tc-99m HMPAO-labelled WBCs and bone scintigraphy as a combined technique to improve specificity in diagnosis of bone and soft tissue infections.Materials and Methods: This study included 65 sites suspected to have bone infection were included. Patients were divided into two major groups; Group A: 16 sites with current endo-prosthesis; Group B: 49 sites with no prosthesis.Images of labeled leukocyte were acquired at 3 different time points after the injection of the labeled leukocytes: 30 min, 2 h, and 4 h. Also all patients had triple phase bone scan. Results: The overall sensitivity for bone scan for detection of osteomyelitis was 100 % but it had a very low overall specificity of only 6.4%. The reported overall sensitivity, specificity and accuracy for Labeled WBCs were 91.1 %, 93.5% and 92.3% respectively. 99mTc-HMPAO labeled WBCs showed better sensitivity, specificity and accuracy in the group with prostheses reaching 100%, 91.6% and 93.7 % respectively. Whereas, the sensitivity, specificity and accuracy of the triple phase bone scan were 100%, 7.6%, and 31.25% respectively. In the group with no prosthesis, the sensitivity, specificity and accuracy of the labeled WBCs modality were 90 %, 94.7%, and 91.8% respectively. While the sensitivity, specificity and accuracy of the triple phase bone scan were 100%, 5.2% and 63.2% respectively. Conclusion: 99mTc-HMPAO-leukocyte appears to be an effective and sensitive and the most accurate modalities that it is superior to triple phase bone scan in assessment of bone infection that help the patients to avoid unnecessary invasive diagnostic and therapeutic procedures.