This study was designed to evaluate the effects of alprostadil on patients with refractory heart failure receiving statin treatment. One hundred patients with refractory heart failure were categorized into two groups, control (n = 50) and intervention (n = 50). The control group was treated with statins only, while the intervention group received a combination treatment with alprostadil and statins. Total effective rate, New York Heart Association (NYHA) functional classification, quality of life (QOL) score, ventricular remodeling indices, oxidative stress indices, inflammatory factor index, and the serum levels of B-type natriuretic peptide (BNP), blood lipid, blood glucose, and insulin were compared between the two groups. The total effective rate of the intervention group was significantly higher than that of the control group. Following treatment, the intervention group experienced more significant improvements in terms of NYHA functional class, QOL scores, ventricular remodeling indices, oxidative stress indices, and serum levels of inflammatory factor, BNP, blood lipid, blood glucose, and insulin compared with the control group. Administration of alprostadil to patients with refractory heart failure receiving statin treatment can increase the total effective rate; down-regulate serum levels of inflammatory factor, BNP, blood lipid, and blood glucose; and improve insulin resistance, illustrating its value in this clinical application.