Background: Previous studies have linked some BRCA1/2 mutations with increased incidence and poor overall survival (OS) in prostate cancer (PCa). In this study both BRCA genes were screened for germline mutations in a larger cohort of PCa and mutation status was correlated with PCa prognostic factors (PFs). Methods: 3818 patients (pts) were enrolled in the UK Genetic Prostate Cancer Study (UKGPCS) between1990-2005. Inclusion criteria for our analysis were available genomic DNA and clinical and survival data in our prospectively maintained UKGPCS database. Genomic DNA was screened for BRCA1/2 mutations. The Kaplan-Meier method and Cox Regression models were used to study the association between BRCA mutation carrier status and other PCa PFs with OS, cause specific OS (CSS), and metastasis free survival (MFS). Results: 2181 pts were eligible for analysis. Median age was 57yrs (range 32-89). BRCA1 and BRCA2 mutations were detected in 5 and 34 patients respectively. BRCA2 tumors were associated with higher histologic grade (Gleason≥8: BRCA2 50%, BRCA1 20%, Non carriers [NC] 21%; p=0.017), nodal disease (N1: BRCA2 35%, BRCA1 50%, NC 11%; p<0.001), metastasis (M1: BRCA2 21%, BRCA1 20%, NC9%, p=0.034) and advanced stage (BRCA2 62%, BRCA1 50% NC18%, p<0.001). Median OS for BRCA2 was significantly inferior to NC (10.8 vs 13.3 yrs, respectively, HR 2.5, p<0.001). The later difference was greater when analyzing CSS (8.6 vs 16.3 yrs, HR 2.8, p<0.001). PFs for CSS in the multivariate analysis (MVA) included stage and PSA doubling time but not BRCA2 per se (HR 1.9, CI95% 0.7-6.7). BRCA2 pts had a worse 10 yrs MFS rate than NC (63% vs 86%, HR 3.6, p=0.001). Median OS from M1 was not significantly different between BRCA2 and NC (2.8 vs 3.4 yrs, p=0.7). BRCA1 pts had a shorter median OS and CSS (10.6 yrs) than NC (p=0.14 and p=0.09), but this trend was lost in the MVA. Conclusions: Our results confirm that PCa pts with BRCA mutations have a poor outcome. Both BRCA1 and BRCA2 mutation carriers with PCa are more likely to have nodal involvement and metastasis at diagnosis and earlier disease progression. OS and CSS are significantly lower in men with BRCA2 mutations.These data should be taken into account in the screening and management of BRCA mutation carriers.