30 patients affected by Rheumatoid Arthritis were treated with Methotrexate (5-7.5 mg/weekly) per os and followed up for at least 12 months; 10 patients had a further control at 24 months. 27 subjects were also on corticosteroid and 2 patients did not stop the therapy with second line drugs. Sulindac was allowed. 3 months later it was observed a significant reduction in the number of affected joints, in the duration of morning stiffness, in the dose of steroid and an improvement of the laboratory investigations indicating the activity of the disease. In the following 12 months, in the 25 subjects still in the study, there was a further clinical improvement. In 24-months follow-up, side effects were present in 17 patients (56.7%); only in 4 cases it was necessary to stop therapy with Methotrexate (3 cases for hepatotoxicity, 1 case for leukocytopenia and stomatitis). 3 subjects did not respond to therapy and 3 patients interrupted for psychological distress. This study confirms the efficacy of Methotrexate at low doses in the treatment of Rheumatoid Arthritis and the modest incidence of severe side effects.