The aim of the study was to compare the effectiveness of hyaluronic acid (HA) injection and arthrocentesis plus HA injection for treating disc displacement with reduction (DDwR) and disc displacement without reduction (DDwoR). In this randomized clinical trial, patients were divided into 2 main groups: group I (DDwR) and group II (DDwoR). Sub-groups were made depending on allocated treatment: group Ia (arthrocentesis plus HA), group Ib (single HA), group Ic (control), group IIa (arthrocentesis plus HA), group IIb (single HA), and group IIc (control). The primary outcome variable was maximum pain on chewing, while maximum pain at rest, maximum non-assisted and assisted mouth opening, chewing efficiency, temporomandibular joint (TMJ) sounds, quality of life, treatment tolerability, and treatment effectiveness were secondary outcomes. The influences of individual study variables (gender, involved side, and duration of symptoms) on clinical outcomes were also examined. The study consisted of 116 TMJs of 90 patients (n = 45 in both main groups, TMJs = 58) aged 15-82 years. At the 6-month follow-up, improvement in all parameters, except for TMJ sounds, was recorded in all treatment groups, with no improvements in control groups. Notably, arthrocentesis plus HA showed superior improvement in chewing efficiency (p = 0.041) and quality of life (p = 0.047) of group I and quality of life (p = 0.004) in group II, compared to single HA. Furthermore, the duration of symptoms correlated with clinical outcomes. Both procedures successfully improved the symptoms of DDwR and DDwoR patients, but arthrocentesis plus HA injection seemed superior.