Objective <p>The aim of this study was to compare the therapeutic outcomes of single versus multiple injectable platelet-rich fibrin (i-PRF) injections after arthrocentesis in patients with temporomandibular joint osteoarthritis (TMJ-OA). The objective was to evaluate and compare TMJ pain and mobility at the 1st, 6th, and 12th months postoperatively.</p> Methods <p>This retrospective cohort study included 85 female patients (age: 31–73 years, mean ± sd: 54.9 ± 8.8) who underwent arthrocentesis with i-PRF injections from June 2018 to November 2021, diagnosed with osteoarthritis based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Patients had no prior use of occlusal splint. During follow-up visits, pain was evaluated with a visual analog scale (pVAS) during function and maximum interincisal opening (MIO) was measured to assess jaw mobility. The study included patient follow-up records at four time points: preoperative (T0), 1 month postoperative (T1), 6 months postoperative (T2), and 12 months postoperative (T3). The primary outcome variable was pVAS at T3, secondary outcome variables were pVAS at T1 and T2, and MIO at T1, T2, and T3.</p> Results <p>No significant differences were found in joint pain or mobility between groups at follow-ups (&gt; 0.05).</p> Conclusions <p>Both groups showed similar outcomes in terms of pain and mobility over a 12-month period. Increasing the frequency of i-PRF injections does not appear to have an impact on therapeutic outcomes in patients with TMJOA. Given the retrospective design of this study, it is important to evaluate the results with caution.</p>