Background: Ra-223 is an alpha emitter that selectively targets BM. It was shown to improve the survival of patients (pts) with CRPC and BM, and thus is approved as a standard tx for these pts. However, the imaging response during Ra-223 tx is poorly defined. We aimed to describe the imaging response in pts with CRPC and BM treated with Ra-223. Methods: We evaluated the CT and bone scans response among pts with CRPC and BM, who were treated with Ra-223. Tx consisted of an injection administered q 4 weeks up to 6 injections. Scans were done at baseline, after 3 injections, and upon completion of 6 injections. Logistic regression model was used to analyze clinicopathologic factors associated with scans response. Results: 51 pts were included (median age 72). 59% (n = 30) were treated post docetaxel chemotherapy. 47% (n = 24) were treated concomitantly with a systemic standard therapy (e.g enzalutamide or abiraterone). 76% (n = 39) completed the planned 6 injections. A clinical benefit (improvement of skeletal pain and performace status) was noted in 67% (n = 34). 53% (n = 27) had a decrease of alkaline phosphatase. The response of bone metastatic disease (number of lesions) at 3 months was improvement in 22% (n = 11), stable in 53% (n = 27), and progression in 25% (n = 13). 1/13 (8%) pts evaluated at 6 months, had a progression of BM versus the 3 months status. Progression (RECIST ) of extraskeletal sites (lymph nodes, lungs, liver, adrenal) at 3 months was noted in 35% (n = 18). Concurrent systemic standard therapy (e.g enzalutamide or abiraterone) (OR 3.3, p = 0.04), Pre-tx PSADT ≥ 3 months (OR 2.62, p = 0.02) and on treatment stable/decreasing LDH (OR 2.9, p = 0.05) were associated with on treatment stable extraskeletal metastatic disease. Conclusions: Progression of BM during Ra-223 was uncommon. A bone flare may be noted during the first 3 months, and should not be confused with BM progression. Clinician should consider repeating a CT scan at 3 months in pts with short pre-tx PSADT, and LDH increase during tx, to exclude extraskeletal metastatic disease progression.