Background <p>The utilization of 3D printed custom guides for arthrocentesis is scarcely discussed in literature and the recent introduction of injectable Platelet Rich Fibrin (i-PRF) has sparked considerable debate in managing temporomandibular joint dysfunction (TMD).</p> Objective <p>The aim of this single blinded, comparative, randomized trial was to compare the clinical outcome of arthrocentesis with intra-articular i-PRF injection using conventional method or CT-guided 3D printed patient-specific template in treatment of TMJ dysfunction.</p> Methods <p>Twenty patients were randomly divided into two groups: 10 underwent conventional arthrocentesis (CA) and 10 underwent arthrocentesis using a 3D-guided template (CTG). In both groups, intra-articular i-PRF was injected in three sessions at one-week intervals. Operative duration, pain scores (Wisconsin Brief Pain Questionnaire), maximum inter-incisal opening (MIO), lateral movements, and clicking were recorded pre-operatively and at 1 week, 1 month, 3 months, and 6 months. Successful joint access, confirmed by visualization of Ringer’s lactate efflux, was noted in 70% of the CA group and in none of the CTG group. At the 6-month follow-up, the CA group showed lower pain scores and better mouth opening and jaw movement, with clicking resolved in 90% compared to 60% in the CTG group.</p> Results <p>Conventional arthrocentesis with i-PRF demonstrated more reliable intra-articular access and superior clinical improvement, whereas the guided approach yielded critical insight into procedural variables including imaging acquisition parameters, template stability, and fabrication workflow that directly influence accuracy of needle trajectory. The study also highlights i-PRF as a beneficial biologic adjunct in TMJ internal derangement.</p> CTRI Registration <p>CTRI/2022/09/045728 dated 21/09/2022.</p>