Aim of the work: To investigate the serum interleukin-20 (IL-20) level in rheumatoid arthritis (RA) patients and to elucidate its relationship with disease activity and ultrasonographic (US) findings. Patients and methods: 45 RA patients and 45 matched controls were enrolled. Modified health assessment questionnaire (mHAQ) and disease activity score (DAS-28) were determined. Power Doppler (PD) and Gray-scale (GS) US evaluation was made using German US7 score. Serum IL-20 level was analyzed using an enzyme-linked immunosorbent assay. Results: Mean age of patients was 34.5 +/- 11 years; 39 females and 6 males and disease duration 15.8 +/- 8.3 years. Their mean DAS-28 was 4.1 +/- 1.1. The serum IL-20 levels were highly significant in patients (30.2; 19.1-58.5 ng/l) than in controls 13.1; 11-15.1 ng/l; p < 0.001). Serum IL-20 significantly correlated with DAS-28 (r = 0.32, p = 0.03), mHAQ (r = 0.87, p < 0.001), erythrocyte sedimentation rate (r = 0.82, p < 0.001), C-reactive protein (r = 0.32, p = 0.03), and disease duration (r = 0.87, p < 0.001). Significant correlations were found between IL-20 level and German US7 variables including synovitis (PD: p = 0.02 and GS: p = 0.01), tenosynovitis (PD: p = 0.01 and GS: p = 0.01) and erosion (p = 0.02) scores. Only morning stiffness, tenosynovitis GS score, tender joint count and mHAQ were significant predictors of IL-20 serum level (p = 0.045, p = 0.04, p = 0.03 and p = 0.001 respectively). Serum IL-20 at cut-off point of 15.4 ng/l could significantly distinguish patients from controls (AUC = 0.89; sensitivity 82.2%, specificity 77.8% and accuracy of 80%; p < 0.001). Conclusion: Patients with RA exhibited a significant elevation in IL-20. Serum IL-20 level significantly correlated with disease activity and ultrasound variables and may serve as a potentially effective biomarker in the evaluation of disease activity in RA. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of Egyptian Society for Joint Diseases and Arthritis This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).