Objective To evaluate the cardiovascular (CV) complications associated with orchiectomy (OE) and parenteral polyestradiol phosphate (PEP) therapy (240 mg/month), taking into account the effect of pretreatment diseases and pretreatment medication. Material and methods A total of 244 T3-4 M0 patients and 200 T1-4 M1 patients were randomized to either OE or PEP therapy. The two groups of patients were analyzed separately. The follow-up period was 36 months. The effect of pretreatment vascular and other diseases and pretreatment medication which may be associated with a risk of CV complications was evaluated. Results In the T3-4 M0 patients, the treatment (PEP versus OE) and the presence of pretreatment vascular diseases were statistically significantly associated with a risk of CV complications (p=0.01 and 0.003, respectively). In the T1-4 M1 patients, such an association was not found. No association was observed between pretreatment medication and CV complications. There was no difference in progression-free time between the therapy groups in either the T3-4 M0 or T1-4 M1 patients. Conclusion In patients with locally advanced prostatic cancer, PEP therapy is associated with a statistically significantly higher risk of CV complications compared to OE.