Purpose: We investigated the effect of tumor location (anterior vs posterior) on pathological characteristics and biochemical-free survival in patients with a preoperative prostate specific antigen level of greater than 20 ng/ml undergoing radical prostatectomy since transition zone tumors are known to present with higher prostate specific antigen levels. Materials and Methods: We retrospectively studied the records of 265 patients treated with radical prostatectomy between 1984 and 2005 who had preoperative prostate specific antigen levels greater than 20 ng/ml. Review of pathology reports was performed and tumor location (anterior vs posterior) was defined. Differences in clinicopathological characteristics and prostate specific antigen recurrence rates were examined. Results: Of 265 patients with a preoperative prostate specific antigen level of greater than 20 ng/ml who underwent radical prostatectomy 50 (19%) had anterior tumors and 215 (81%) had posterior tumors. Patients with anterior tumors had lower clinical stage and less seminal vesicle involvement than patients with posterior tumors (p = 0.006 and <0.001, respectively). Although Kaplan-Meier analysis demonstrated significantly higher rates of 5-year biochemical recurrence-free survival for patients with anterior vs posterior tumors (63% vs 40%, p = 0.020), anterior tumor location was not an independent predictor of biochemical recurrence. Conclusions: Radical prostatectomy is a feasible treatment option in patients with a preoperative prostate specific antigen level of greater than 20 ng/ml. The 5-year biochemical-free survival rate was 47%. Although anterior tumor location was associated with favorable pathological features and improved biochemical-free survival, it was not an independent predictor of biochemical recurrence. Further studies are warranted to identify patients with high preoperative prostate specific antigen levels most likely to have recurrence. © 2007 American Urological Association.