Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. It's role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively. PSA response, PSA progression-free survival (PSA-PFS) and overall survival (OS) from mCRPC to death were analyzed using Kaplan-Meier curves, Log-rank test, Cox regression models and Harrell's C-index. The incidence of IDC-P in mCRPC reached 47.3%. IDC-P was not only related to rapid PSA progression, but also associated with a 20-month decrease in OS. Among IDC-P(-) patients, PSA response, PSA-PFS and OS were comparable in abiraterone-treated and docetaxel-treated groups. In contrast, among IDC-P(+) patients, PSA response rate is higher in abiraterone-treated group vs. docetaxel-treated group (52.4% vs. 21.7%; p = 0.035). Also, PSA-PFS and OS were much longer in the IDC-P(+) abiraterone-treated group vs. the docetaxel-treated group (PSA-PFS: 13.5 vs.6.0 months, p = 0.012; OS: not reach vs.14.7 months, p = 0.128). Overall, IDC-P in mCRPC from re-biopsy was an independent prognosticator for clinical outcome. Abiraterone was observed having a better therapeutic efficacy than docetaxel as the first-line therapy in IDC-P(+) mCRPC patients. Thus, we suggest IDC-P should be considered as a novel predictive marker helping physicians making treatment decisions for mCRPC.