The cardiovascular benefits of marine-derived omega-3 fatty acids are supported by epidemiologic and clinical studies. Both healthy patients and those with confirmed coronary heart disease are advised by the American Heart Association to consume omega-3 fatty acids either through dietary fatty fish or fish oil products. We present two case reports of patients with dyslipidemia who were switched from an omega-3 dietary supplement or a prescription omega-3 drug containing eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) to a new prescription EPA-only drug, icosapent ethyl (IPE). Products containing a combination of EPA and DHA, including dietary supplements and prescription products, are more likely to increase low-density lipoprotein cholesterol (LDL-C) levels compared with pure EPA-only products. The lipid profiles of these two patients were improved with IPE treatment, illustrating the potentially favorable effects of IPE compared with other products containing both EPA and DHA.