Introduction: We present the results of a study by the Pharmacology and NeuroHumoral Activation Registry (FAR NHL), which collects data on patients with chronic heart failure. The register contains 1088 patients from three workplaces in the Czech Republic which specialize in the care of patients with heart failure. Objectives: The aim was to obtain a comparison of pharmacotherapy and the incidence of comorbidities in patients with reduced ejection fraction (HFrEF) versus patients with mid-range (or newly mildly reduced) ejection fraction (HFmrEF). Methods: Patients with a baseline left ventricular ejection fraction below 50% were included and divided into HFrEF with EF below 40% and HFmrEF with EF 40–49%, according to the 2016 ESC Guidelines. In addition to the clinical condition, we also monitored laboratory parameters, comorbidities and pharmacotherapy in the patients. Results: Patients with HFrEF versus HFmrEF are more likely to be male (p < 0.008), younger (p < 0.001), have lower systolic blood pressure and are less likely to have ischemic etiology of heart failure (p < 0.001). There were no differences between the groups in the proportion of comorbidities: hypertension, diabetes mellitus, dyslipidemia, ischemic lower limb disease or chronic obstructive pulmonary disease. There were no differences in the proportion of smokers and non-smokers between the groups. Patients with HFrEF have a higher class of New York Heart Association (NYHA), a level of N-terminal fraction of natriuretic peptide B (NT-proBNP), and a higher level of urea and uric acid. They are more often treated with loop diuretics or mineral corticosteroid receptor (MRA) blockers and less often with thiazides (p < 0.001), and also have a worse two-year prognosis. Conclusion: Compared to patients with HFmrEF, patients with HFrEF have more severe heart failure, more pronounced neurohumoral activation and a worse prognosis. They do not differ in the presence of comorbidities.