Background: Hyperkalemia is a common electrolyte disorder in patients with heart failure and reduced ejection fraction (HFrEF). Renin-angiotensin-aldosterone system inhibitors (RAASi) have been shown to improve survival and decrease hospitalization rates, although they may increase the serum potassium levels. Hyperkalemia has significant clinical and economic implications, and is associated with increased healthcare resource utilization. The main objective of this study was to analyze the management of hyperkalemia and the associated medical costs in a cohort of patients with HFrEF. Methods: An observational, longitudinal, retrospective, single-center retrospective study was made in patients with HFrEF who started follow-up in a specialized heart failure unit between 2010 and 2021. Results: The study population consisted of 1181 patients followed-up on for 64.6 ± 38.8 months. During follow-up, 11,059 control visits were conducted, documenting 438 episodes of hyperkalemia in 262 patients (22.2%). Of the hyperkalemia episodes, 3.0% required assistance in the Emergency Department, 1.4% required hospitalization, and only 0.2% required admission to the Intensive Care Unit. No episode required renal replacement therapy. Reduction or withdrawal of RAASi was necessary in 69.9% of the hyperkalemia episodes. The total cost of the 438 hyperkalemia episodes was €89,178.82; the expense during the first year accounted for 48.8% of the total cost. Conclusions: Hyperkalemia is common in patients with HFrEF. It is often accompanied by a modification of treatment with RAASi. Hyperkalemia generates substantial costs in terms of healthcare resources and medical care, especially during the first year.