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Background and Aims: It has been reported that elevated serum uric acid (SUA) is related to inflammation and potentially to platelet hyper-reactivity. However, the relationship between elevated SUA and residual platelet reactivity is uncertain in patients on dual antiplatelet treatment (DAPT) with aspirin and clopidogrel., Methods and Results: A cross-sectional cohort study was conducted on 2569 patients undergoing DAPT with aspirin and clopidogrel. Patients' SUA levels, residual platelet aggregation, routine blood tests and clinical characteristics were recorded. The relationship between SUA level and residual platelet aggregation was assessed by correlation analysis, and the relationship between SUA level and the prevalence of clopidogrel low response (CLR) was assessed by multivariate logistic regression analysis. Adenosine diphosphate (ADP) induced platelet aggregation (PL ADP ) was higher in normal-SUA group than that in hyperuricemia group [30(21, 40) % vs. 27(19, 39) %, p = 0.032]. No significant difference was found for arachidonic acid (AA) induced platelet aggregation (PL AA ) between the two groups [4(2, 5) % vs. 3(2, 5) %, p = 0.557]. The correlation between SUA and PL ADP was statistically significant(r = -0.115, p < 0.001), while that between SUA and PL AA was non-significant (r = -0.012, p = 0.643). Using the multivariate logistic regression analysis, higher SUA concentration was associated with a decreased risk of clopidogrel low response (CLR) (OR [95%CI] = 0.997 [0.995-0.999], p = 0.001)., Conclusion: This is the largest study to date showing that in patients receiving DAPT with aspirin and clopidogrel, SUA is independently and negatively associated with the prevalence of clopidogrel low response., Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique Identifier: NCT01955200., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)