TMJDs (Temporomandibular joint disorders) are a common pathology but best treatment remains unclear. The goal of this study was to evaluate the effectiveness of mesotherapy on TMJD. We conducted a case review of all TMJD patients treated since 2006 with mesotherapy procedures only and using a cocktail of drugs composing of lidocaine, piroxicam and pentoxifylline. Patients were treated every 15 days until symptomatic relief was achieved and thereafter every two months. Main outcome was complete symptomatic relief, and associated factors were analysed. 27 patients were included. Complete pain relief was achieved in 26. The necessary number of procedures to get pain relief ranged from 1 to 6 (median of 1) and the total number of treatments from 1 to 40 (median of 11). 19 patients had other painful complains mainly related with anxiety disorders. A weak correlation (r = 0.357; p = 0.05) between anxiety disorders and the required months of treatments was found. Mesotherapy is a valuable option on pain relief in a temporomandibular pain syndrome with none of the systemic effects of oral medication. Anxiety may have a role on the aetiology and therapeutic success highlights the holistic approach of these patients. Future comparative studies are necessary.