ContextThe treatment of high-risk prostate cancer requires a multimodal approach to improve control of the disease. There is still no consensus as to the initial strategy of choice. The aim of this study is to review the results of radical prostatectomy as first step in management of patients with high-risk disease. Acquisition of evidenceA search was conducted on PubMed of English and Spanish texts. We included those studies that reported the results of radical prostatectomy in patients with high-risk prostate cancer, as well as those that compared radical prostatectomy with other treatment alternatives. The last search was conducted in November 2015. Synthesis of the evidenceThe advantages of radical prostatectomy include a better pathological analysis, more accurate staging, better local control of the disease and better follow-up and adjuvant therapy strategies. When compared with external radiation therapy plus hormonal blockade, the patients who underwent prostatectomy had greater chances of healing and longer cancer-specific survival. The patients who most benefit from this approach are younger, have fewer comorbidities and no evidence of organ metastases. ConclusionsThe available scientific evidence to date is not without bias and confounders; however, they appear to favor radical prostatectomy as the initial approach of choice for high-risk prostate cancer.