Purpose: Prospective observational study to determine the role of 18F-FDG-PET/CT in evaluation of musculoskeletal tuberculosis Methods: 15 patients diagnosed with primary musculoskeletal tuberculosis clinico-radiologically or histopathologically underwent whole body 18F-FDG-PET/CT prior to start of ATT, after 6 and 12 months of ATT along with clinical assessment and clinical parameter (pain, swelling, tenderness and overall clinical score including these three) was compared to disease response on 18F-FDG-PET/CT after continuation of ATT at 6- and 12-months follow-up. Also, response of disease (both skeletal and extra skeletal lesions) was compared on subsequent follow-up on 18F-FDG-PET/CT quantitatively. Results: After 6 months of treatment, response in pain was high however high metabolic activity persisted on 18F-FDG-PET/CT (kappa value 0.191). However, when metabolic activity compared with overall clinical score, there was a fair agreement (kappa value 0.271) between these two. Similarly, when it was compared after 12 months, there were a total disagreement (kappa value - 0.024) between the responses of pain, tenderness and overall assessment with metabolic activity on 18F-FDG-PET/CT. There was significant decrease in disease activity of extra skeletal lesions after 6 months of ATT (p value 0.024) with response noted in more than 80% lesions. Conclusion: 18F-FDG-PET/CT can detect early response and residual disease in skeletal and extra-skeletal tuberculosis in comparatively asymptomatic patient even up to 18 months treatment and can be used to modify treatment period. It has high ability to detect extra-skeletal lesions in skeletal tuberculosis and so can be used for extent of disease.