Purpose: This study aimed to analyze the overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with either combination or only secondary hormone therapy (2ndHTx) or docetaxel chemotherapy. Materials and Methods: Between 2005 and 2018, 307 mCRPC patients’ medical records were retrospectively reviewed treated with either 2ndHTx (HTx [N=73, 23.8%] either abiraterone acetate or enzalutamide), docetaxel+2ndHTx (CTx-HTx [N=90, 29.3%]) or only docetaxel therapy (CTx-only [N=144, 46.9%]). The Cox proportional hazard model for risk factors of OS and Kaplan-Meier analysis with log-rank test for OS comparison among three therapeutic groups with a statistical significance of p＜0.05. Results: During a median 49.6-month follow-up and a median 22 months of OS, the worst OS was observed in CTx-only (17.7 months) followed by the CTx-HTx (22.9 months), and only-HTx (42.6 months) groups (p＜0.001). The baseline comparison showed that age, body mass index, TN stagings, and prostate specific antigen level were significantly different between groups (p＜0.05). In the multivariable analysis for the risk factors of OS, age (hazard ratio [HR], 0.978), cT3–4 stage (HR, 1.606), and HTx (HR, 0.482) were significant factors. With the HTx agents, enzalutamide was the only left risk factor for OS regardless of underlying diseases (HR, 0.511; p＜0.001). The group analyses for the OS showed that only-CTx group (HR, 2.696) and CTx-HTx group (HR, 1.434) were unfavorable factors for OS with a reference of HTx group (p＜0.001). Conclusions 2ndHTx was a significant prognostic factor for OS regardless of underlying diseases in patients with mCRPC and improved OS in comparison with docetaxel.