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We assessed the impact of prostatic zone tumor origin on pathological prognostic features and subsequent biochemical outcomes after radical prostatectomy.A total of 7,051 patients who underwent radical prostatectomy between September 1998 and December 2016 in Western Australia were divided into a high grade group, defined as Gleason sum 4 + 3, 8 and 9 or greater and ISUP (International Society of Urological Pathology) groups 3, 4 and 5, and a low grade group, defined as Gleason sum 6 or less and 3 + 4, and ISUP groups 1 and 2. The t-test and the Pearson chi-square test were used to evaluate differences between transition zone and peripheral/central zone cancer. The Kaplan-Meier method with the log rank test was used to determine differences in biochemical recurrence-free survival at 5 years in patients with high grade disease. Univariate and multivariable Cox proportional hazard regression analyses were performed. Model calibration was determined by the internal validation method.High grade transition zone cancer was associated with significantly increased prostate specific antigen, tumor volume and incidence of positive surgical margins but a lower incidence of intraductal carcinoma, extraprostatic spread, seminal vesicle invasion, lymph node involvement and biochemical failure after radical prostatectomy. Patients with low grade prostate cancer had excellent biochemical recurrence-free survival regardless of tumor origin. The high grade multivariable model had a c-index of 0.78 and improved predictive accuracy, particularly for high grade transition zone disease.Transition zone tumor origin independently and positively impacts biochemical outcomes of high grade prostate cancer. A high grade postoperative prognostic model including transition zone tumor origin as an independent predictor was developed and predictive accuracy was significantly improved in patients with high grade, transition zone disease.