Objective: To assess the pain relief after denosumab use in grade III giant cell tumor of bone (GCT-B). Study Design: Retrospective Cohort study. Setting: Department of Orthopedic Surgery Dow University of Health Sciences / Dr Ruth KM Pfau Civil Hospital Karachi. Period: 2018 May to 2020 June. Material & Methods: Total 27 patients were included in the study with diagnosis of grade III GCT-B. Patients with Stage I & II excluded from study. Results: After the first dose of Denosumab, 24 (88.9%) patients reported no pain relief while the other 3 (11.1%) patients had mild pain. A second dose of Denosumab was given to these patients. After the second dose, 3 (11.1%) patients scored mild pain and 24 patients had a score of ≥4 on VAS. The pain severity reduced significantly after administration of 2nd dose of Denosumab (p=0.019). Pain severity was remeasured after the third dose of Denosumab where they had VAS of 0 to 6, with inconsistent use of simple analgesics. The pain severity reduced significantly after administration of 3rd dose of Denosumab (p=0.001). Conclusion: We conclude that denosumab have excellent analgesic effect in grade III giant cell tumor of bone. We recommend the use denosumab in perioperative therapy for grade III GCT-B bone and we found analgesic effect as additional one. It may gain some time for patient specially in developing nations where oncology surgery centers are limited. It also reduces the use of NSAIDS during window period of definitive surgery.