Background: Radium 223 Dichloride (223Ra) has been shown to improve overall survival in men with metastatic Castration-Resistant Prostate Cancer (mCRPC) with symptomatic bone metastases. Pain is the most common symptom developed by patients (pts) with bone metastases with psychological status impairment. Our aim was to evaluate the psychological distress, (such as functional status, social support, anxiety and depression), and trend of pain response during 223Ra treatment. Methods: Our current clinical experience accounts for 39 pts affected by mCRPC and bone metastases. A total of 118 cycles were administred with 50 KBq/Kg i.v. q4w of 223Ra. Mean age was 75,2±6,07. Gleason Score average value was 8 and ECOG Performance Status mean value was 1,48. Pts were evaluated with Brief Pain Inventory (BPI 0-10 Scale) and data were collected. To examine quality of life (QoL) endpoints, pts were asked to complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the bone metastasis module, QLQ-BM22. Both were submitted at baseline and after every cycle of therapy. Edmonton Symptom Assessment Scale (ESAS) was used with the same timing to evaluate response to treatment. Results: 39 pts underwent 1 cycle of therapy with 223Ra. Of these 43% had psychological distress, with an average value of 7,6 in BPI Scale for pain outcome. Second cycle was administered to 33 pts. Pain mean value of these pts was 7,13 and psychological distress was present in 35%. The evaluation of functional scales after third cycle showed that of 29 pts, 32% had psychological distress with a pain average value of 6,4. Analyzing pts that underwent 6 cycles showed that 27% present psychological distress and the mean value of BPI was 5,6. Conclusions: 223Ra therapy shows a multidimensional impact on quality of life, in particular as regards psychosocial aspects. In patients with painful bone metastases from CRPC there is a strong direct relationship between pain reduction and improvement of the subjective psychological distress.