Denosumab is a human monoclonal antibody used to prevent skeletal-related events in prostate cancer patients with bone metastasis. Hypocalcemia ranging from mild to severe requiring prolonged hospitalization have been reported with the use of denosumab in patients with known risk factors such as chronic kidney disease, vitamin D deficiency, low parathyroid hormone level, hypomagnesemia, extensive osteoblastic metastasis, prior use of bisphosphonates, and comorbidities impairing calcium absorption. We present a case of a metastatic prostate cancer patient with extensive osteoblastic metastasis who developed severe recurrent hypocalcemia after a single dose of denosumab requiring a total of 58 days of high dose intravenous and oral calcium supplementations with three inpatient hospital admissions. This case highlights the risk of severe hypocalcemia associated with denosumab use even after the disease control with oncologic therapy and in the absence of other predisposing risk factors. This case also emphasizes monitoring calcium levels closely in all patients treated with denosumab. In the event of severe hypocalcemia, prolonged hospitalization should be expected, and discharge planning should be done meticulously, which may help decrease the overall length of hospital stay, readmissions, and morbidity.