Background: Internal derangement (ID) is the most common cause for TMDs. Various invasive, minimally invasive, and non-invasive treatment modalities have been attempted. Arthrocentesis as a minimally invasive maneuver either if followed with various intra-articular medications or not has been attempted to treat ID. Hyaluronic acid (HA) has been used as an intraarticular medication due to its lubricant effect that improves joint movement and mechanically reduces friction pain. However, the i-PRF had both anti-inflammatory action to reduce the level of the cytokines; aided by the regenerative capacity to the torn and degenerated tissues of the joint including the synovial tissue. Purpose: The current study aimed at comparing both factors. Materials and Methods: Forty TMJs from thirty patients were randomly divided into two equal groups. In group I, arthrocentesis was followed by intra-articular injection of AH; however, in group II, arthrocentesis was followed i-PRF injection. Results: In general, group II patients recorded better results with respect to clicking, pain, and movement limitation. Superior results of i-PRF might be the result of the regenerative capability that not only reduced the existing inflammatory mediators; but also replaced the degenerated cytokines-releasing tissues by healthy synovial fluid-releasing tissues provides endogenous sustained source of HA. Conclusion: Although both treatments are acceptable, i-PRF was a rather recommended treatment.