Background: Autoantibodies are the hallmark of autoimmune diseases. For Rheumatoid arthritis (RA), they represent equipment for prognosis, detection and analysis of the disease. Several serological markers have recently emerged. For instance, serum Anti-PADI4 that is the enzyme that causes citrullination of proteins leading to autoantibodies production. The goal of this work was to assess the role of peptidyl arginine deiminase type 4 (PADI4) in diagnosis of rheumatoid arthritis and association of its serum level with disease activity. Methods: A case-control study involving 58 subjects, 29 patients with RA and 29 healthy controls matched in age and sex, was carried out at Department of Rheumatology and Rehabilitation, Zagazig University Hospitals. Detailed history taking, clinical examination and assessment of disease activity using: - DAS-28, modified HAQ, CRP, ESR and PGA. Serum Anti-PADI4 was measured in RA patients and healthy controls using quantitative ELISA technique. Results: Statistical analysis of the obtained clinical and laboratory data showed a significant elevation of serum Anti-PADI4 in RA patients 15.39±8.89 ng/ml when compared to controls 6.32±10.3* ng/ml (P