Objectives: To retrospectively assess the outcome of patients with initial PSA of 20 ng/ml or higher undergoing radical prostatectomy (RP) I-or prostate cancer (pCA) Methods: Between January 1986 and June 2005, 275 patients with preoperative PSA >= 20 ng/ml underwent RP for pCA at our institution. Overall, disease -specific and biochemical progression -free survival rates for the entire cohort and for particular subgroups were determined. Results: Median patient age at time of surgery was 64 yr (range: 44-75). Fifty-seven patients (20.7%) had pT2 stage, 206 (74.9%) pT3, and 10 (3.7%) pT4; 78 (28.4%) presented with local nodal metastases (pN+). To date, 40 patients have died (14.5%), 22 of pCA and 18 of other causes. Biochemical progression occurred in 92 patients (33.5%). Overall (and disease-specific) survivals at 5, 10, and 15 yr were 87% (93%), 70% (83%), and 58% (71%), respectively. These survival rates did not significantly differ between patients receiving immediate versus deferred hormonal therapy (in case of progression). Five-year PSA progression- free survival in patients on surveillance (receiving deferred hormonal treatment at the onset of rising PSA values) was 53%. For patients on immediate hormonal treatment following RP, the 5-yr hormone-refractory PSA progression rate was 76%. Conclusions: According to long-term follow-up results in this high-risk cohort of patients with preoperative PSA >= 20 ng/ml, RP can be considered a viable therapeutic option. With regard to combining immediate hormonal therapy with surgery, the optimal treatment following RP remains to be defined.