Introduction: Etelcalcetide has proven effective and well tolerated in the treatment of secondary hyperparathyroidism (IPS) in patients on hemodialysis (HD). Since long-term studies are scarce, we assessed the efficacy and safety of etelcalcetide in the treatment of severe IPS in a group of HD patients over a 12-month period. Patients and Methods: We selected 24 HD patients with PTH levels > 500 pg/mL (range 502-2148 pg/mL), despite following a therapy with cinacalcet and/or vitamin D analogues. The initial dosage of etelcalcetide was 7.5 mg/week, then it was adjusted based on the trend of the levels of the total albumin-corrected serum calcium (CaALb_c) and PTH. Treatment was temporarily suspended if CaALb_c levels were <7.5 mg/dL or if hypocalcemia was symptomatic. CaALb_c, phosphorus, PTH and total alkaline phosphatase (t-ALP) were measured monthly. The main endpoint was the decrease in PTH levels >30% compared to baseline values. Results: At F-U, the reduction in PTH levels was > 30% in 83% of our patients. PTH levels decreased from 1169 ± 438 to 452±241 pg/mL at F-U (P <0.001). The percentage of reduction in PTH levels at F-U was -56 ± 25%. CaALb_c and phosphate levels decreased from 9.8 ± 0.4 mg/dL to 9.0 ± 0.6 mg/dL (P <0.001), and from 6.1 ± 1.3 mg/dL to 4.9 ± 1.3 mg/dL (P <0.01), respectively. The main side effect was hypocalcaemia, but never so severe as to require the interruption of treatment. Hypocalcemia was more pronounced in patients with higher basal levels of PTH and t-ALP. During the study, the percentage of patients treated with calcium carbonate increased from 33% to 54% and that of patients treated with paricalcitol from 33% to 79%. At F-U the average weekly dosage of etelcalcetide was 21.0 ± 9.5 mg (range 7.5-37.5 mg/week). Conclusions: The treatment of severe IPS with etelcalcetide has been proved effective and safe in the long term. Hypocalcaemia, the most frequent side effect, was more evident in patients with the most severe forms of IPS and was probably due to a reduction in bone turnover rather than to the direct effect of etelcalcetide.