Abstract: We analyzed clinical effects of flutamide as a second-line agent for maximum androgen blockade (MAB) in patients with relapsing prostate cancer who received bicalutamide as the first-line MAB agent. This study included 13 patients with progressive prostate cancer who had relapsed after first-line MAB, with bicalutamide at 80 mg/day. After checking for antiandrogen withdrawal syndrome, they were given flutamide at 375 mg/day as second-line MAB. The effectiveness of that therapy was evaluated by changes in prostatic specific antigen (PSA) levels, with response defined as a decrease of greater than 50% from the start of therapy. We also compared several factors between responders and non-responders. Nine (69.2%) of the 13 patients showed a decrease in PSA levels, of whom five (38.5%) had a greater than 50% decrease and were defined as responders. The median duration of PSA response was 11.0 months (range 5–20 months). Patients who had a longer duration of response to first-line MAB had a significantly greater response to second-line MAB. For advanced prostate cancer patients who progressed on first-line MAB with bicalutamide, flutamide administration as a second-line antiandrogen was found to be relatively effective, especially for those who showed a longer duration of response to the first-line MAB. Our results confirm previous findings that MAB using flutamide is an effective second-line hormonal therapy.