Objective <p>To investigate the effect of sacubitril/valsartan (ARNI) combined with cardiac rehabilitation (CR) in patients with heart failure (HF) after acute myocardial infarction (AMI).</p> Methods <p>A total of 118 patients with HF after AMI were screened and randomly divided into an experimental group and a control group. The control group was given ARNI. The experimental group received CR treatment in addition to the control treatment. The primary endpoint was cardiorespiratory fitness as measured by the cardiopulmonary exercise test (CPET). The secondary endpoints included cardiac remodeling detected by NT-ProBNP and cardiac ultrasound. All participants were assessed by CPET, NT-ProBNP, and cardiac ultrasound at baseline and after treatment.</p> Results <p>After treatment, the changes in the left ventricular ejection fraction (LVEF), anaerobic threshold (AT), oxygen uptake peak (VO₂ peak), and metabolic equivalents (METs) in the experimental group were significantly greater than those in the control group (all <i>P</i> &lt; 0.05). However, there was no significant difference in BNP, Left atrial diameter (LA) or Left ventricular end diastolic diameter (LVD) between the two groups (<i>P</i> &gt; 0.05).</p> Conclusions <p>Patients with HF after AMI could benefit from combined ARNI and CR.</p> Trial registration <p><a href="http://www.chictr.org.cn">http://www.chictr.org.cn</a>, ChiCTR2400093772 (11/12/2024). Retrospectively registered.</p>