The aim of the study was to evaluate overall and prostate cancer (PCa) specific survival with special attention to cardiovascular (CV) mortality in patients primarily treated by parenteral polyestradiol phosphate (PEP) 240 mg/month or with orchiectomy (OE), taking into account the effect of pretreatment diseases and medication, and later PCa therapies. The present Finnprostate 6 study (10-year follow-up) consisted of 244 patients with locally advanced PCa (T3-4 M0) and 200 patients with metastatic PCa (T1-4 M1). Patients were randomized to OE or PEP therapy. The T3-4 M0 and T1-4 M1 patients were analyzed separately. There was no difference in overall or PCa specific survival between the primary therapy groups in T3-4 M0 or T1-4 M1 patients. In the T3-4 M0 patients the primary treatment (PEP vs. OE) was statistically significantly associated with a risk of CV deaths (P = 0.001). Such an association was not found in the T1-4 M1 patients. The primary PEP and OE therapies are equal in terms of overall and PCa specific survival in patients with T3-4 M0 or T1-4 M1 disease. In T3-4 M0 patients PEP increases the risk of CV deaths compared to OE but not in T1-4 M1 patients.