OBJECTIVE To examine the safety and efficiency of using Peg-IFNα2a/ribavirin and low-dose NSAID therapy in patients with rheumatoid syndrome (RS) and chronic hepatitis C (CHC). METHODS A group of 10 patients (group 1) known to have RS and established CHC undergoing Peg-IFNα2a/ribavirin and low-dose NSAID therapy was compared with a control group of 10 patients (group 2) also with CHC and associated RS, with no antiviral treatment. Their charts were reviewed for serological and clinical signs of rheumatic disease evolution while undergoing this type of treatment. RESULTS At the end of a follow-up period of 12 months, patients receiving low-dose NSAID and Peg-IFNα2a/ribavirin therapy showed a sustained virusological response and also decreased levels of inflammation serological markers, with an improvement in the clinical rheumatic symptoms. In contrast, patients in group 2 showed no significant clinical modification in their rheumatic status. CONCLUSION Peg-IFNα2a/ribavirin and low-dose NSAID in patients with RS and CHC appear to be well tolerated and can be efficient for rheumatic manifestations. Further controlled studies are required to confirm the results.