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Background: The current study aimed to evaluate the effect of the time duration to reach the lowest prostate-specific antigen (PSA) from the onset of first-line hormonal treatment (time to nadir PSA, TTNpsa) on survival in castration-naive metastatic prostate cancer (CN-MPC) patients. Methods: Eighty patients who had PSA response >80% with first-line hormonal therapy (luteinizing hormone-releasing hormone, LH-RH analog +/- bicalutamide) were included in this study. Results: Under androgen deprivation therapy (ADT), a significant positive correlation was found between TTNpsa, nadir PSA (Npsa) duration, and progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). There was no correlation between TTNpsa and Npsa duration. TTNpsa and Npsa durations were independently correlated with PFS and OS. In patients with TTNpsa value ≥19 weeks, the median PFS was 126 (95% CI, 68–184) weeks compared with TTNpsa <19-week group in which the median PFS was 44 (95% CI, 26–62) weeks (p = 0.033). In patients with TTNpsa value ≥19 weeks, the median OS was 242 (95% CI, 169–315) weeks compared with TTNpsa <19-week group in which the OS was 156 (95% CI, 89–223) weeks (p = 0.018). The median nadir PSA value was 1 ng/mL. The median PFS was significantly longer in the patient group with ≤1 ng/mL (137 weeks, 95% CI, 50–224) compared with the group with >1 ng/mL (41 weeks, 95% CI, 34–48) (p < 0.001). The median OS was significantly longer in the patient group with nadir PSA ≤1 ng/mL (296 weeks, 95% CI, 220–272) compared to the group with >1 ng/mL (131 weeks, 95% CI, 84–178) (p = 0.002). In patients with nadir PSA ≤1 ng/mL (n = 40), there was no relationship between TTNpsa and Npsa duration with both PFS and OS. However, in patients with nadir PSA >1 ng/mL (n = 40) subgroup, there was a significant positive correlation between TTNpsa and PFS, and OS (p < 0.001, P = 0.016, respectively). Conclusion: In CN-MPC who received first-line ADT, especially in the group with the nadir PSA value >1 ng/mL, the duration of TTNpsa was positively correlated with PFS and OS. [ABSTRACT FROM AUTHOR]