In a prospective, interventional study on efficacy and safety of alfacalcidol (1?D3) treatment of rheumatoid arthritis (RA), 67 patients with active RA were included, treated for at least three months before inclusion with the highest tolerated dose of methotrexate (MTX), with no associated disease or therapy of influence to inflammation or calcium metabolism. After signing the written consent, samples were taken for biochemical and immunoserological testing, also urine for daily calciuria, activity of RA, functional status, life quality, fatigue, muscle strength and function were assessed, bone mass and quality were examined. Patients were randomly assigned to treatment with 1 µg, 2?g, 3?g 1?D3 daily or 20 mg of prednisone daily for the first month, and 10 mg during the next two months. They were monitored at 2-4 week for insight into the efficacy and safety of treatment used. After the completion of this research period, clinical and laboratory data obtained were compared with initial ones in each group, as well as to each other. All patients continued investigation taking 1µ 1?D3 daily, for 9 months. Three months treatment either 1 µg, 2?g, 3?g 1?D3 or prednisone significantly decreased RA activity and in 1?D3 2?g subgroup to improved functional ability, physical and mental quality of life, muscle power and coordination, reduction of biochemical parameters of inflammation, interleukin 6, increase of HDL cholesterol, with moderate increase of daily calciuria. At the end of follow up, the loss of bone mass was found in patients treated with prednisone, yet improvement of the quality of the bone in alfacalcidol treated ones.