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Abstract Background Bempedoic acid is an oral cholesterol-lowering medication used to reduce low-density lipoprotein cholesterol (LDL-C), particularly in patients who require additional lipid lowering. Clinical trials have shown that bempedoic acid increases serum uric acid levels, but the implications of this effect in real-world clinical practice, including the need for anti-gout treatment, are not well defined. Methods We conducted a retrospective cohort study using a large, multi-institutional U.S. electronic health record database. Adult patients with hyperlipidemia who have newly initiated bempedoic acid were compared with those initiating ezetimibe. Propensity score matching was used to balance baseline characteristics, yielding 7676 patients in each group. The primary outcome was incident hyperuricemia, defined as serum uric acid >7.0 mg/dL. A secondary outcome was initiation of anti-gout therapy. Results During 12 months of follow-up, hyperuricemia occurs more frequently in patients treated with bempedoic acid than in those receiving ezetimibe (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.58–2.37; p = 0.008). In contrast, initiation of anti-gout therapy does not differ between groups (HR 1.06; 95% CI 0.86–1.29; p = 0.59). Longitudinal changes in lipid parameters, inflammatory markers, and glycemic measures are generally similar between groups. Conclusions In real-world clinical practice, bempedoic acid use is associated with a higher incidence of laboratory-defined hyperuricemia compared with ezetimibe, but this increase does not translate into greater use of anti-gout medications. These findings support the continued use of bempedoic acid for additional LDL-C lowering, with awareness of its effect on serum uric acid.