Background: Bone metastases (mets), present in >90% of patients (pts) with CRPC, may cause severe pain. In a phase II dose-response study with Ra-223 treatment, pain response (pain reduction and stable analgesic consumption) was seen in up to 71% of CRPC pts with painful bone mets (Nilsson 2012). In the phase III ALSYMPCA study, which included 921 CRPC pts with bone mets randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching placebo (Ra-223, n=614; placebo, n=307), Ra-223 significantly improved overall survival vs placebo (median 14.9 vs 11.3 mo; HR=0.695) and was well tolerated. Post hoc analyses of pain parameters in ALSYMPCA are presented. Methods: The hazard ratios for time to initial opioid use and time to external beam radiation therapy (EBRT) were analyzed using the Cox proportional hazards model. Pts with no opioid use at baseline were included in the pain analyses. Concomitant opioid use was recorded from first study drug injection to 12 weeks after last injection. Results: Baseline pain characteristics were similar between the treatment groups (approximately 55% of pts had moderate to severe pain and opioid use based on WHO ladder for cancer pain). Time to EBRT was significantly longer in the Ra-223 group vs placebo (HR=0.670, 95% CI: 0.525-0.854). Fewer Ra-223 pts reported bone pain as an AE compared to placebo pts (50% vs 62%). 269 pts in the Ra-223 group and 139 pts in the placebo group had no opioid use at baseline. Median time to initial opioid use was significantly longer in the Ra-223 group, with a risk reduction of 38% compared to placebo (HR=0.621, 95% CI: 0.456-0.846). Fewer pts in the Ra-223 group (36%) than in the placebo group (50%) required opioid use for pain relief. Conclusions: These ALSYMPCA results provide consistent evidence that, in addition to prolonging survival, Ra-223 reduces pain and opioid use in patients with CRPC and bone metastases. Clinical trial information: NCT00699751.