Objective To investigate the clinical efficacy ofω-3 unsaturated fatty acid enteral nutrition (EN) for treatment of elderly patients with heart failure (HF). Methods One hundred and twenty six elderly patients with HF admitted to Hangzhou Geriatric Hospital from April 2013 to April 2018 were enrolled to be the study objects, and they were divided into a TPF group and a TPF-T group (63 cases in each group) according to the difference in nutrition preparation. The nasal feeding with EN solution rich in ω-3 unsaturated fatty acid was applied in the TPF-T group; while in the TPF group, nasal feeding with common EN solution was given. According to the body mass quantity to calculate the necessary heat standard, the target energy established for the two groups was 104.6-125.5 kJ·kg-1·d-1. The changes of levels of albumin (Alb), prealbumin (PA), transferrin (TRF), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), T lymphocyte subsets such as CD3+, CD4+, CD8+, CD4+/CD8+, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), and left ventricular ejection fraction (LVEF) were observed in the two groups before and after treatment, and the prognostic indexes and incidence of adverse reactions of the two groups were also observed. Results After treatment, the levels of Alb, PA, TRF, and the immune function indexes CD3+, CD4+, CD8+, CD4+/CD8+ were significantly increased in both groups (all P < 0.05), while the serum levels of IL-6, hs-CRP, TNF-α and NT-proBNP were obviously decreased in both groups (all P < 0.05), moreover, the degrees of changes in the above parameters in the TPF-T group were more significant than those in the TPF group [Alb (g/L):36.91±4.49 vs. 36.31±3.95, PA (mg/L): 190.26±15.39 vs. 188.51±17.62, TRF (g/L): 2.31±0.44 vs. 2.25±0.71, IL-6 (ng/L): 312.53±42.69 vs. 372.45±51.25, hs-CRP (mg/L): 20.43±15.72 vs. 35.81±14.28, TNF-α (ng/L):81.36±17.32 vs. 152.67±21.71, CD3+: 0.59±0.06 vs. 0.55±0.05, CD4+: 0.33±0.05 vs. 0.28±0.04, CD8+:0.23±0.03 vs. 0.21±0.04, CD4+/CD8+: 1.55±0.34 vs. 1.36±0.41, NT-proBNP (ng/L): 149.00±0.38 vs. 242.00±0.56, all P < 0.05]; the intensive care unit (ICU) length of stay, the total hospital length of stay in the TPF-T group were significantly shorter than those in the TPF group [ICU length of stay (days): 9.41±3.19 vs. 12.39±3.75, total hospital length of stay (days): 15.24±4.63 vs. 18.26±5.18, both P < 0.05], and the incidence of adverse reaction in TPF-T group was lower than that in the TPF group: [4.76%(3/63) vs. 17.46% (11/63), P < 0.05]. However, there was no statistical significant difference in left ventricular ejection fraction between the TPF-T group and TPF group (LVEF: 0.418±0.053 vs. 0.417±0.052, P > 0.05). Conclusion Early application of ω-3 unsaturated fatty acid EN may improve the immunologic function of T lymphocytes as well as prognosis, reduce the inflammatory response in elderly patients with HF, and reduce the incidence of adverse reactions.