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Rheumatoid arthritis is a symmetrical autoimmune chronic polyarthritis, that affects about 1% of the population around the world, its multifactorial causes include environmental, genetic, and epigenetic, invading both sexes mostly females, and all ages. Early detection of the disease may serve to avoid bone damage. The study aimed to assess the disease activity of RA by using biomarkers ACCP, CTHRC1, IL-6, and Cystatin-D and detect their accuracy in RA diagnosis. This study concluded that a total of 150 blood samples were Collected, 100 RA patients and 50 healthy Control. throughout the period from November 2021 to February 2022. The RA patients were diagnosed depending on the 2010 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR). The blood sample was collected from the Baghdad Teaching Hospital / Rheumatology Consulting Clinic. General information had been collected from each individual according to a questionnaire that had been applied for this purpose. The age group of patients and control was 22-72 years and 26 -62 years respectively. The female was more than the male. The blood sample was taken from patients and controls groups to screen ACCP, IL-6, CTHRCI, and cystatin D, these tests were done by ELISA methods ACCP, IL-6, CTHRC1, and Cystatin D, and they were highly significant at a P-value of 0.00 for all. The association between cystatin D and CTHRCI with CDAI levels appeared in most patients was a high percentage with a moderate level of CDAI at 56.6 % and 51.7 % respectively. The result was highly significant at a P-value of 0.00, while the ACCP and IL-6 association with CDAI levels appeared most of the patients were high percentage with moderate levels of 48.9% and 47.4% respectively, but the result was non-significant at a P-value > 0.05. The correlation between the CDAI according to its score depended on the cutoff points appeared that ACCP, CTHRC1, and cystatin D were significant, this indicated that these parameters can be used as definitive diagnostic parameters for RA patients depending on the ROC. The Roc appeared the sensitivity for ACCP, CTHRC1, and Cystatin-D was 0.98, 0.87, and 0.89 respectively. while the specificity was 0.98, 1:00, and 0.98 respectively.