Our pilot study aimed to investigate the efficacy and tolerability of intra-articular (i.a.) injections of infliximab as a therapy for erosive osteoarthritis of the hands. Ten women with bilateral involvement of the hands and typical erosive osteoarthritis radiographic findings were enrolled and followed for 12 months. All the patients were refractory to conventional drugs. Treatment consisted in monthly i.a. injections of 0.2 ml of infliximab (0.1 mg/ml) in each affected proximal and distal interphalangeal joint of the most involved hand, identified on the basis of clinical and radiological examinations. The other hand was treated with physiological saline (control). The patients did not know which hand was receiving infliximab. Clinical response was evaluated at enrollment, after 6 and 12 months. Posteroanterior radiographs of both hands were obtained at baseline and 12 months later. At 6 months all the patients experienced relief from spontaneous pain and pain on lateral pressure in the hand treated with infliximab and these findings became statistically significant after 1 year. No important modifications were recognized in the hand treated with physiological saline. The anatomical lesion progression system radiological score indicated a reduction, even if not statistically significant, in the hand treated with infliximab and a tendency to slow worsening in the hand treated with physiological saline at 12-month follow-up. No local or systemic adverse reactions were recorded. Our study shows the symptomatic effect and a possible disease modifying action of i.a. infliximab in erosive osteoarthritis of the hands.