Background: There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). Methods: The clinical chart of 233 CRPC patients treated with enzalutamide was reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were classified to whom introduced with full dose of enzalutamide or whom with reduced dose and the oncological outcomes were compared. To investigate the independent predictive factors with progression-free survival (PFS) and overall survival (OS), univariate and multivariate Cox regression analyses were performed.Results: Of total, 190 CRPC patients initiated with full dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between full and reduced dose group. The incidence rate of patients with prostate specific antigen (PSA) decline of >90% in reduced dose group was significantly lower than that in full dose group (34.8% vs46.2%) (p-value 0.03). The incidence rates of AEs were not statistically different between reduced dose group (22.6%) and full dose group (34.4%) (p-value 0.24). On multivariate analyses, initial enzalutamide dose was not a predictive factor of PFS and OS. Conclusion: Initiating with reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed less PSA response rate. There is no clear rationale of treating with initial reduction of enzalutamide resulted in overcome incidence of AEs.