Objectives: To explore the rationale for ω-3 fatty acids in heart failure treatment, the dosage of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) for replacing low levels of highly unsaturated fatty acids (HUFA deficiency) was examined. To judge the usefulness of various EPA/DHA preparations, their content of peroxides and aldehydes was determined. Methods: In 298 patients with dilative heart failure, the serum HUFA level was assessed by gas chromatography. In ω-3-acid ethyl esters 90 (Omacor/Lovaza, approved by the Food and Drug Administration and the European Medicines Agency) and 63 dietary supplement fish oils, oxidation products were determined by photometry. Results: Increasing serum HUFA from the lower (4.3 ± 1.0%) to the upper (9.5 ± 1.5%) tertile would be associated with an increased left ventricular (LV) ejection fraction (34.1 ± 9.9 vs. 28.3 ± 9.5%, p < 0.01) and reduced LV enddiastolic diameter (63.5 ± 7.1 vs. 66.9 ± 7.4 mm) requiring at least 2 g EPA/DHA daily. In fish oils, the peroxide and alkenal level varied greatly, i.e. peroxide value ≤5 mEq/kg in only 7 and ≤10 mEq/kg in 38 fish oils. Compared with equivalent doses of ω-3-acid ethyl esters 90, the mean peroxide intake would be 8.6 ± 6.1 and the alkenal intake 10.9 ± 4.4 times higher in fish oils. Conclusions: Levels of adverse oxidation products should be considered when targeting HUFA deficiency or treating patients with myocardial infarction or high triglycerides.