There is no effective standard therapy for the treatment of hormone-refractory prostate cancer (HRPC), and treatments vary among different medical institutions with efforts to improve results. The present retrospective investigation was performed to assess the outcomes of second line, third line, and fourth line therapies. A total of 142 patients with HRPC were treated at Nagoya City University Hospital and its affiliate hospitals during the 10 years between October 1996 and August 2006. Patient background and treatments given after hormone refractory phase were determined, with especial attention to 50% or greater decrease rates of serum PSA levels and other variables with three common regimens based on: estramustine phosphate (EMP); diethylstilbestrol diphosphate (DES); and dexamethasone (DEX). With second line therapy for HRPC, the response rate was highest with EMP, whereas best outcomes were apparent with DES as a third line or fourth line therapy. However, overall survival for all cases and particularly with those having a poorly differentiated lesion, was best with EMP in any time period. Although there is no generally established optimal treatment for HRPC, our analysis supports the efficacy of EMP based on second line therapy response rates and optimal prognosis with longer term use.