Background: Prognostic models of OS in men with metastatic castrate-resistant prostate cancer (M+CRPC), have been limited. Here we present an analysis of baseline covariates associated with OS from an international phase 3 study that demonstrated superiority of denosumab over zoledronic acid for prevention of skeletal-related events (SRE) in this population (Fizazi et al., Lancet 2011;377:813-822). Methods: Patients had confirmed bone metastases (BM) from CRPC (a rising PSA despite castrate testosterone levels) and no prior bone anti-resorptive therapy. Proportional hazards modeling with various selection strategies was used to assess the prognostic significance of baseline covariates in multivariate analyses. Study-specified factors (previous SRE [Y vs N], PSA level [<10 vs ≥10 ng /mL]) and additional variables (Cook et al., Clin Cancer Res 2006;12:3361-3367; Halabi et al., J Clin Oncol 2003;21:1232-1237; Halabi et al., J Clin Oncol 2008;26:2544-2549) were explored. As no difference in OS was observed between treatment arms, analyses were performed using the pooled overall patient population. Results: Analyses included all randomized subjects with available baseline covariate data (n=1745). At the primary analysis date (median study duration 12.2 months), OS was 51%. Various selection strategies produced consistent results. In multivariate analysis, bone-specific alkaline phosphatase (BAP) ≥146 μg/L (p<0.0001) and corrected urinary N-telopeptide (uNTx) >50 nmol/mmol (p=0.0008) were associated with shorter OS, as were prior SRE (p=0.0002), PSA ≥10 ng /mL (p<0.0001), visceral metastases (p=0.0002), greater time from either diagnosis to first BM or first BM to randomization (p<0.0001 for both), ECOG performance status 2 vs. 0/1 (p=0.017), BPI-SF pain score >4 (p<0.0001), age (p=0.008), alkaline phosphatase >143 U/L (p<0.0001), and hemoglobin ≤128 g/L (p<0.0001). Conclusions: Besides known factors previously associated with OS in men with CRPC (Halabi et al., 2003), we show that bone-associated covariates (pain, prior SRE, BAP, and uNTx) are also important and independent prognostic factors for OS.