Limited data exist on the long-term safety and efficacy of bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor, for lowering low-density lipoprotein cholesterol (LDL-C). This 78-week, phase 3, open-label extension (OLE) study followed the CLEAR Harmony phase 3 study, in which patients were randomized 2:1 to bempedoic acid or placebo for 52 weeks; during the OLE, patients who received bempedoic acid continued treatment (≤130 weeks) and patients who received placebo initiated bempedoic acid (≤78 weeks). Safety assessments included treatment-emergent adverse events, adverse events of special interest, and clinical laboratory abnormalities. Efficacy assessments included % change from the parent study baseline in LDL-C, other lipid parameters, and high-sensitivity C-reactive protein (hsCRP). Of 1,462 patients who enrolled in the OLE study, 970 received bempedoic acid in the parent study; laboratory abnormalities and reductions in LDL-C, other lipid parameters, and hsCRP observed in the parent study remained stable through 130 weeks of treatment. On initiation of bempedoic acid treatment, 492 patients who received placebo in the parent study experienced reductions in LDL-C, other lipid parameters, and hsCRP, mirroring reductions observed in patients who received bempedoic acid in the parent study who remained stable through 78 weeks of therapy. During the OLE, incidence of treatment-emergent adverse events and adverse events of special interest were comparable in patients who received 130 weeks (78%) versus 78 weeks (78%) of bempedoic acid treatment. In conclusion, bempedoic acid was generally well tolerated and demonstrated sustained efficacy with up to 2.5 years of continuous treatment. Bempedoic acid safety profiles were similar between the parent and OLE studies.