Background:Temporomandibular disorder (TMD) is a musculoskeletal disorder within the masticatory system. The present study was conducted to compare theefficacy of arthrocentesis alone and arthrocentesis withduloxetine in patients with TMJ pain. Materials & Methods:40 patients with TMJ pain were randomly divided into two groups of 20 each. Group I patients were treated with arthrocentesis alone and group II with arthrocentesis followed by duloxetine 30 mg twice daily for 12-week therapy. Patients were followed up at regular interval at day 1, day 5, day 7, week 4, week 6 and week 12. Outcome assessment of pain and maximal mouth opening was done. Results: There were 8 males in group I and 9 in ii and 12 females in group I and 11 in group II.VAS score in group I was 5.1, 5.8, 4.9, 4.5, 3.5, 3.3 and 3.0 and in group II was 6.0, 6.5, 4.3, 4.0, 3.2, 2.8 and 1.6 at Pre- op, day 1, day 5, day 7, week 4, week 6 and week 12 respectively. The maximum mouth opening (mm) pre- op, day 1, day 5, day 7, week 4, week 6 and 12 weeks was 34.2, 35.6, 38.4, 40.6, 41.2, 41.9 and 42.5 in group I and 35.4, 36.7, 38.9, 40.5, 42.6, 43.7 and 45.2 in group II respectively. The difference was significant (P< 0.05). Conclusion:Combination of duloxetine witharthrocentesis gave much better outcome than arthrocentesis alone in TMJ pain patients.