The aim of the present investigation was to compare the effectiveness of six treatment protocols providing TMJ arthrocentesis with or without additional drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease over a three-months follow up period. Different combinations of single-needle and two-needle arthrocenteses, alone or with injection of corticosteroids or hyaluronic acid immediately following the joint lavage, were adopted in 72 patients. The protocol providing five weekly low-molecular weight hyaluronic acid injections, immediately following a classical two-needle arthrocentesis, was superior to all the other treatments to reduce pain-related symptoms in patients with inflammatorydegenerative TMJ disease. This was even if treatment effects were not significantly different with respect to those achieved with other protocols. Keywords: arthrocentesis, inflammatory-degenerative disease, hyaluronic acid, temporomandibular joint, temporomandibular disorders