The 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) and the 2021 European Society of Cardiology (ESC) both provide evidence-based guides for the diagnosis and treatment of heart failure (HF). In this review, we aimed to compare recommendations suggested by these guidelines highlighting the differences and latest evidence mentioned in each of the guidelines. While the staging of HF depends on left ventricular ejection fraction, the Universal Definition of HF, suggested in 2021, is described in 2022 ACC/AHA/HFSA guidelines. Both guidelines recommend invasive and non-invasive tests to diagnose. Despite being identical in the backbone, some differences exist in medical therapy and devices, which can be partially attributed to the recent trials published that are presented in the American guidelines. The recommendation of implantable cardioverter defibrillator for prevention in HF with reduced ejection fraction (HFrEF) patients, made by ACC/AHA/HFSA guidelines, is among the bold differences. It seems that ACC/AHA/HFSA guidelines emphasize the quality of life, cost-effectiveness, and optimization of care given to patients. On the other hand, the ESC guidelines provide recommendations for certain comorbidities. This comparison can guide clinicians in choosing the proper approach for their own settings and the writing committees in addressing the differences in order to have better consistency in future guidelines.