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Cardiovascular disease remains a significant global health burden. Bempedoic acid is a novel, oral adenosine triphosphate-citrate lyase inhibitor that lowers low-density lipoprotein cholesterol (LDL-C). While randomized controlled trials (RCTs) have established its efficacy and safety, evidence from real-world clinical practice is needed. A systematic literature review (SLR) was conducted to identify studies reporting real-world use of bempedoic acid as monotherapy, in fixed dose combination with ezetimibe, or in combination with any other lipid lowering therapy (LLT). MEDLINE, EMBASE, and Cochrane Library were searched from inception to February 19, 2025. Two reviewers independently screened studies, with discrepancies resolved by a third. Data extraction and validation were conducted, and the risk of bias assessed using the Newcastle–Ottawa Scale. Of 269 records, 28 reports on 22 unique studies met the eligibility criteria. Most studies evaluated LDL-C changes from baseline after initiation of bempedoic acid; one pragmatic randomized trial was identified. Bempedoic acid achieved LDL-C reductions of 15% to 39% when added to maximally tolerated statins, 22% to 38% in statin intolerant cohorts, and 18% to 42% in mixed statin intolerant cohorts. Safety data was limited; treatment discontinuation ranged from 9% to 36%, with higher rates in cohorts with greater statin-intolerance. This SLR shows bempedoic acid, with or without other LLTs, achieves a minimum of approximately 20% LDL-C reductions, consistent with RCTs. Data suggests it may be effective as an adjunct to statins and as an oral alternative for statin-intolerant patients. • Real-world bempedoic acid achieved ≥20% LDL-C reduction in routine practice. • LDL-C lowering was consistent across statin-treated and statin-intolerant cohorts. • The magnitude of LDL-C reduction was broadly consistent with RCT evidence. • No new safety concerns emerged, although safety reporting was limited.