Background : Articular involvement is a frequent extrahepatic manifestation of hepatitis C virus (HCV) infection. The distinction between HCV associated arthropathy and oncomitant rheumatoid arthritis (RA) may be very difficult, especially with recent onset RA before articular damage and erosions develop. This study aims to determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are a highly specific test for RA, could differentiate between chronic HCV-associated arthropathy and RA with concomitant HCV. Methods: Three patients' groups were included. Group I: patients with chronic HCV infection without arthropathy, Group II: patients with chronic HCV infection with arthropathy and to compare the prevalence of anti-CCP antibodies in HCV patients with that in patients with RA and concomitant HCV we enrolled 22 (Group III) consecutive RA patients fulfilling the American College of Rheumatology (ACR) revised criteria for Rheumatoid arthritis and the new EULAR / ACR criteria with concomitant HCV. Twenty two healthy controls (Group IV) were also included. For each group anti-CCP antibodies and rheumatoid factor were measured. Results: Anti-CCP antibodies were positive in 4.5% , 4.5%, 100% and 0% of groups I to IV respectively. However, RF was positive in 13.6% , 45.5%, 100% and 0% of Group I to IV respectively. Anti-CCP antibodies showed higher specificity compared with RF (97% vs. 80%) in the diagnosis of RA, but the two tests had similar sensitivity (100%). Conclusions: Measurement of anti-CCP antibodies is more specific than RF to discriminate HCV-associated arthropathy from RA with concomitant HCV. Moreover it may contribute in establishing the diagnosis of RA in patients with concurrent chronic HCV infection