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Background and Objective: Rheumatoid arthritis is a chronic, inflammatory and systemic disease with peripheral, symmetric polyarthritis symptoms. Several genetic, environmental, and immunological factors contribute greatly to the disease pathogenesis. This study was done to evaluate the effect of anti-cyclic citrullinated peptide (anti - CCP) and rheumatoid factor on clinical disease activity index (CDAI) in the patients with rheumatoid arthritis. Methods: This prospective cohort study was done on 64 rheumatoid arthritis patients according to ACR criteria (1978) whom referred to Rheumatology Clinic of Hajar Hospital in Shahrekord, Iran. Patients were clinically examined for primary CDAI and tested for anti - CCP and rheumatoid factor in the prior and six months after the initiation of the study. Results: 81.3% and 74% of the patients had high titers of anti – CCP antibody and positive rheumatoid factor, respectively. A non-significant recudtion was observed in intensity of secondary clinical activity of the disease in compare to primary clinical activity in the patients with high antibody titer. Conclusion: This study indicated the important role of rheumatoid factor and anti- CCP antibody in the on time diagnosis of rheumatoid arthritis.