OBJECTIVES: Prostate cancer represents the 2nd most common cause of cancer mortality[1]. Clinical studies showed that chemotherapy (CT) had survival benefits for Metastatic CRPC[2-6]. This study described 1st-line and 2nd-line CT and investigated OS benefits of 2nd line CT using a real-world data. METHODS: The Georgia Cancer Specialist Database containing CT, medical and pharmacy information, and lab results for patients (PTs) with cancer (2005-2011) was used. PTs greater than 18 years old with initial stage IV CRPC who received one type CT protocol (PL), as first-line group, and two types of PLs, as second-line group, were followed from the first administration of CT (index date, ID) to the earlier of death or loss to follow-up. CT use was described. Kaplan-Meier survival curve was compared between first-line and second-line groups using log-rank test. The impact of second-line CT on OS was further examined using multivariate Cox model with adjustment of PTs’ baseline age, race, Charlson Comorbidity Index (CCI), bisphosphonate use, and ECOG performance scores. RESULTS: The study included 124 PTs, with 86 (69.4%) as first-line PTs,  range in age from 18-90 (median 74 years of age), 52.4% of race White, 32.3%  African American, and 15.3% other or unknown race, average weight was 185LB (ranging 100-365LB), average baseline PSA 731 ng/ml (ranging 0.05-21,743ng/ml), 107(86.3%) PTs with one or more CCI comorbid conditions, 10 (8.1%) PTs with ECOG score as 3 or 4. 96 (77.4%).  Docetaxel was used as first-line CT. Other first-line CT drugs were: Denosumab, vinorelbine, sipuleucel-T,mitoxantrone/Prednisone, and Cisplatin. Second-line CT drugs were: denosumab, Novantrone/Prednisone, Cabazitaxel, and Carboplatin. Median survival was 17 months for all, 14 and 19 months for first-line and second-line PTs, respectively (P=0.0654). Multivariate COX model found a higher survival for second-line PTs (HR=0.361, P=0.010). CONCLUSIONS: This study suggested that second-line CT was associated with prolonged OS in metastatic CRPC.