Purpose: We evaluated the relative risk of biochemical recurrence, metastasis and death from prostate cancer contributed by biopsy Gleason pattern 5 among men at high risk with Gleason 8-10 disease in the SEARCH (Shared Equal Access Regional Cancer Hospital) cohort.Materials And Methods: Men with biopsy Gleason sum 8-10 prostate cancer treated with radical prostatectomy were evaluated. The cohort was divided into men with Gleason 4 + 4 vs those with any pattern 5 (ie Gleason 3 + 5, 5 + 3, 4 + 5, 5 + 4 or 5 + 5). Predictors of biochemical recurrence, metastases, and prostate cancer specific and overall survival were analyzed using Kaplan-Meier, log rank test and Cox proportional hazards models.Results: We identified 634 men at high risk in the SEARCH database, of whom 394 (62%) had Gleason 4 + 4 and 240 (38%) had Gleason pattern 5 on biopsy. Baseline characteristics did not significantly differ between the groups. On multivariable analysis relative to Gleason 4 + 4 men at high risk with Gleason pattern 5 showed no difference in the risk of biochemical recurrence (HR 1.26, 95% CI 0.99-1.61, p = 0.065). However, they were at significantly greater risk for metastasis (HR 2.55, 95% CI 1.50-4.35, p = 0.001), prostate cancer specific mortality (HR 2.67, 95% CI 0.1.26-5.66, p = 0.010) and overall mortality (HR 1.60, 95% CI 1.09-2.34, p = 0.016).Conclusions: Preoperative subclassification of high risk prostate cancer by biopsy Gleason grade (4 + 4 vs any Gleason pattern 5) identified men at highest risk for progression. Any Gleason 5 on biopsy is associated with a greater risk of metastasis, and prostate cancer specific and overall mortality. Grouping all Gleason 8-10 tumors together as high risk lesions may fail to fully stratify men at highest risk for poor outcomes.