Objectives: To assess the efficacy of salmon calcitonin spray on postoperative pain, serum calcitonin levels, and bone healing after surgical removal of impacted mandibular third molar. Materials and Methods: This prospective study included 100 patients who required surgical removal of impacted mandibular third molars under local anesthesia. Group I included 50 patients who received intranasal serum calcitonin spray, and Group II included 50 patients who did not receive serum calcitonin spray. The postoperative pain was evaluated on the 1st, 3rd and 7th days. The serum osteocalcin levels were assessed at 1 month, and bone density was evaluated at the 3rd month postoperatively. Results: The severity of pain was less in Group I on days 3, and 7 postoperatively compared to Group II (P<0.05). The postoperative serum calcitonin level was higher in Group I compared to Group II (P<0.05), and the bone density was greater in Group I when compared to Group II evaluated at the 3rd month postoperatively (P<0.05). Conclusion The results of our study delineate that Group I patients had better efficacy in controlling pain and improved bone healing with calcitonin nasal spray when compared to Group II patients.