Temporomandibular disorder (TMD) includes disorders of the temporomandibular joint (TMJ) and masticatory muscles and their associated structures. It is characterized by pain, joint sounds and restricted mandibular movement. Pharmacological agents commonly used for the treatment of TMDs include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, corticosteroids, muscle relaxants, antidepressants, anticonvulsants and benzodiazepines. Objectives: In the present study, we compared the clinical outcome of intra-articular injections of NSAIDs, corticosteroids, Hyaluronic acid given after temporomandibular joint arthrocentesis. Materials and methods: Twenty-seven patients suffering internal derangement of the temporomandibular joint and not responding to conservative therapy were randomly classified into three equal groups. In group A joint lavage was followed by 1ml of piroxicam injection. In group B joint lavage followed by 1 ml of dexamethasone injection and in group C joint lavage was followed by 1 ml of Hyalgan injection. The treatment outcome was evaluated clinically by measuring the maximal mouth opening in mm at 2 weeks and 3 months postoperatively. Pain was measured using the Visual Analogue Scale at the study intervals. These data were statistically analyzed. Results: All drugs were able to demonstrate a reduction in pain intensity and improvement in mouth opening at 2 weeks and 3 months postoperatively. No significant differences in treatment success were found among the three groups (P > 0.05) through the study intervals. Conclusion: We concluded that arthrocentesis with Piroxicam, dexamethasone or Hyalgan are similarly effective and are promising methods in relieving the symptoms of TMJ with nonreducing disc displacement. Additional prospective studies are required to confirm the adequate dosage of each treatment protocol, frequency of the injections required and combination between those protocols and other modalities in order to achieve long-term results.