Background <p>This study examined to examine the relationship of Epstein-Barr virus (EBV) in rheumatoid arthritis (RA) by evaluating disease activity and autoantibody levels in positive and negative cases using the anti-EBV early antigen diffuse type and restricted type (EA-DR) immunoglobulin G (IgG) antibody.</p> Methods <p>Patients undergoing RA treatment at our hospital with anti-EBV EA-DR IgG antibodies were selected. Patient’s age, sex, RA duration, disease activity, laboratory findings, treatment details, and complications in patients with positive or negative anti-EBV EA-DR IgG antibodies were confirmed, and the relationship between RA activity, autoantibody production, and EBV was analyzed.</p> Results <p>anti-EBV EA-DR IgG antibodies were measured in 70 RA cases (30 positive and 40 negative), with a positivity rate of 43.9%. Among the positive cases, 18 underwent EBV deoxyribonucleic acid polymerase chain reaction, with 14 testing positive. Univariate analysis revealed significantly higher levels of disease activity score in 28 joints with C-reactive protein, peripheral blood lymphocyte count, anti-cyclic citrullinated peptide antibody (ACPA), and rheumatoid factor in anti-EBV EA-DR IgG antibody-positive cases. Multivariate analysis identified peripheral blood lymphocyte count and ACPA levels as significant factors.</p> Conclusions <p>Patients with RA who tested positive for anti-EBV EA-Dr IgG antibodies had significantly higher ACPA than those who tested negative.</p>