Background: The apparent interactions between the mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDS) and steroids suggest that co-therapy may provide beneficial in inflammation and pain relief in the absence of side effects. The aim of the study was to compare the effect of co-administered diclofenac sodium and dexamethasone with diclofenac sodium with tramadol on the postoperative pain, swelling and trismus after surgical removal of third molars. Patients and Methods: A prospective randomized study was conducted at the Chowdhary hospital Bhopal. A total of 100 patients (age range: 20-35 years), with impacted third molar who underwent surgical removal were randomly allocated to two treatment groups. Group A of 50 patients who were given diclofenac sodium (50 mg Oral before and after surgery and dexamethasone (prophylactic 8 mg and postoperative 4 mg IV 8 th hourly) , and Group B of 50 patients who were given diclofenac sodium(50 mg Oral before and after surgery) with tramadol(50 mg orally). Postoperative pain was assessed with a visual analogue scale at 8 th hourly and 3 rd and 7 th postoperatively day (POD). Swelling was measured at 3 and 7th POD Maximal interincisor distance was measured at 3 and 7 POD. Patient treated with diclofenac sodium + dexamethasone showed lower pain score, larger postoperative mouth opening and less swelling compared to diclofenac sodium with tramadol. Results: Co-administration of dexamethasone and diclofenac sodium was significantly superior to diclofenac with tramadol for the relief of pain (P < 0.05), and facial swelling and post operative trismus up to postoperative 48 hour (P < 0.05). Conclusion: This study illustrates enhanced effects of co-administered dexamethasone and diclofenac sodium on short-term post-operative pain and swelling, compared to diclofenac with tramadol in third molar surgery.