The present study aimed to compare the efficacies of intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) following single needle arthrocentesis in patients with TMJ internal derangement. This double-blinded randomised controlled trial involved the enrolment of patients diagnosed with unilateral TMD, falling into either Wilkes' stages II or III. In Group A, single needle arthrocentesis was performed using Ringer's lactate serving as a control group; in Group B, intra-articular injection of 1 ml hyaluronic acid injection was given following arthrocentesis; and in Group C, autologous intraarticular injections of 1 ml of PRP was given after arthrocentesis, twice in two weeks' interval. The primary outcome variables were maximum mouth opening and pain, while TMJ clicking sounds formed the secondary outcome variable. All the outcome variables were assessed preoperatively (T0) and postoperatively after the second dose of injection at one month (T1), three months (T2), and six months (T3). The alpha level was set to p < 0.05. Ninety patients (N = 90) comprised the final sample size of the study with thirty patients(n = 30) in each treatment group. A statistically significant decrease in the management in mean pain scores was noted between T0 [mean scores were 7.30 ± 1.05 (Group A), 7.63 ± 1.12 (Group B), and 7.56 ± 1.04(Group C)] and T3 [mean scores were 2.66 ± 0.88 (Group A), 2.4 ± 0.72 (Group B), and 1.66 ± 0.66 (Group C)] time intervals between Group A and C(p < 0.001). Significant improvement was noted in preoperative maximum mouth opening (MMO) of Group A, B, and C which was 22.83 ± 3.58, 22.17 ± 4.07, and 21.37 ± 3.69, respectively to 28.90 ± 2.72, 32.17 ± 3.97, and 34.10 ± 3.80 mm, respectively at six months postoperatively (p < 0.001). A significant decrease in joint sounds was evident for all three groups(p = 0.003 for Group A, p < 0.001 for Group B, and p < 0.001 for Group C) across the time intervals. Moreover, Group C showed a significant decrease in the prevalence of joint sound compared to the other two groups at all-time intervals postoperatively when equated to baseline (p = 0.02 at T1, p = 0.009 at T2, and p = 0.002 at T3). Within the limitations of the present study, it can be concluded that intra-articular PRP may be preferable over HA whenever appropriate, following single needle arthrocentesis in the treatment of TMJ internal derangement.