Background: In clinical practice, Ra-223 is often combined with Enza or Abi/pred. ERA 223 (NCT02043678) showed increased fracture risk with concurrent Ra-223+Abi/pred. We assessed real-world symptomatic skeletal events (SSEs) and overall survival (OS) of pts with mCRPC who received concurrent or layered Ra-223+Enza or Abi/pred. Methods: Patients with mCRPC treated with Ra-223 in US cancer clinics from 1/01/2013 to 6/30/2017 were identified from a Flatiron prostate cancer registry of electronic health records. Tx initiation defined subgroups: concurrent (both started within 30 days) or layered (1 started ≥30 days after the other). Baseline (BL) was the first dose of Ra-223. Descriptive analysis was performed for BL characteristics, SSEs, and OS (Kaplan–Meier). Results: Of 625 pts treated with Ra-223, 48% received Ra-223+Enza or Abi/pred. Layered Tx was more common (73%) than concurrent (27%). BL characteristics and clinical outcomes were summarized [Table]. Conclusions: Ra-223+Enza or Abi/pred Tx was mainly layered. SSE rates with layered vs concurrent Ra-223+Abi/pred varied between subgroups; results must be treated cautiously given small pt numbers and a non-randomized study. The ongoing PEACE III trial is investigating concurrent Ra-223+Enza; a Phase III study (ESCALATE) exploring layered Ra-223+Enza is planned. Clinical trial information: NCT02043678