Aims: The aim of this study was to explore the utility of 18F-FDG PET/CT in the assessment of response to antitubercular treatment (ATT) and identification of treatment endpoint., Patients and Methods: Forty patients (mean age, 35.3 years; 27 men) with clinically, radiologically, and histopathologically proven joint tuberculosis prospectively underwent clinical, biochemical, and PET/CT evaluation at baseline and after ~6, 12, and 18 months of ATT. Two patients were lost to follow-up, and 1 defaulted treatment. The remaining 37 were followed up until complete response (CR) was achieved. Images were visually and quantitatively (SUVmax ratio and metabolically active disease volume [MV]) evaluated by 2 experienced nuclear medicine physicians., Results: Knee (n = 18) and ankle (n = 7) were the most frequently involved sites. The median MV and SUVmax ratio at baseline were 85.10 mL and 7.21, respectively. Five patients had noncontiguous vertebral involvement, 12 had pulmonary lesions, 2 had abscesses, 6 had mediastinal, and 30 had local lymph nodal involvement. Complete response was seen in 1/39, 11/37, and 30/37 patients after 6, 12, and 18 months of ATT. Significant reductions in visual analog scale score, tenderness, joint swelling, SUVmax ratios, and MVs (Friedman test, P < 0.001) were seen after each follow-up. The median time-to-CR in skeletal lesions was significantly longer than extraskeletal lesions (591 vs 409 days; Wilcoxon signed-rank test, P < 0.001). Time-to-CR in joint lesions positively correlated with MV at first follow-up (Pearson = 0.452, P = 0.005) and negatively correlated with percentage change in MV (first follow-up from baseline) (Pearson = -0.620, P < 0.001). ROC analysis yielded a cutoff of ≤71% reduction in MV at first follow-up (80.8% sensitivity, 81.8% specificity) to predict extension of ATT beyond 12 months. Using ROC analysis at second follow-up, a cutoff of ≤12.67 mL (for CR) was derived and was validated in patients at the third follow-up, with an accuracy of 84.4%. Patients with CR in PET/CT maintained disease-free state during a mean follow-up of 271 days., Conclusions: 18F-FDG PET/CT is an excellent tool in estimating total disease burden, assessing response to ATT and identification of treatment endpoint in joint tuberculosis., Competing Interests: Conflicts of interest and sources of funding: none declared. Compliance with ethical standards: None of the authors or their relatives have any conflicts of interest or any funding sources to disclose. Ethical clearance was obtained (reference IECPG-204, RT-4/28; September 28, 2017) from the ethical committee of our institute, before initiation of this study. This research involves human subjects. Written informed consent was taken from every subject in this study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)