Radium-223 dichloride (Ra-223) is the first bone-targeting agent showing improvement in overall survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases. We aimed to assess feasibility of Ra-223 treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ten patients with primary bone metastases received Ra-223 following radical prostatectomy (RP). Changes in alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were recorded, while pain intensity was evaluated using the self-reporting Brief Pain Inventory (BPI) questionnaire. Bone scintigraphy (BS) was performed to assess treatment response. Seven patients completed six cycles of Ra-223. Discontinuation was due to leuko-and lymphopenia, progressive lymph node metastasis or newly diagnosed liver metastasis. Treatment-related adverse events occurred in three patients and included leuko-and lymphopenia, fatigue, abdominal discomfort and nausea. Overall, a median decrease of 28% in ALP and a median decrease of 83% in PSA were noted at follow-up. However, PSA progressed in five patients at follow-up. Improvement of pain was observed in all patients (median decrease of 36% after 3 cycles and of 40% at the end of therapy). On BS, three patients showed remission, four had stable disease, and one showed progressive disease at follow-up. Our results suggest that Ra-223 for primary bone metastases in patients with mHSPC after RP is feasible and alleviates pain. ALP, rather than PSA, may be a good marker for assessing treatment response. Ra-223 could therefore be taken into consideration as part of a multimodal approach for carefully selected patients with advanced prostate cancer.