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<i>Background and Objectives</i>: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. <i>Materials and Methods</i>: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. <i>Results</i>: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (<i>p</i> < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (<i>n</i> = 122) was 0.62 (±0.55) nmol/L, with low dose (<i>n</i> = 113) 1–39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (<i>n</i> = 202) 40–79 mg/day was 0.72 (±0.34) nmol/L, with high dose (<i>n</i> = 58) 80–119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (<i>n</i> = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, <i>p</i> < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (<i>p</i> < 0.001) according to multivariant analysis. <i>Conclusions</i>: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.