Background: Accurate riskstratification after diagnosis of prostate cancer (PCa) is key to optimal treatment decision-making. Decipher is an extensively validated genomic classifier of metastasis after radical prostatectomy (RP). Here, we evaluate its ability to predict metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens in a cohort of intermediate risk PCa patients treated with RP. Methods: Fifty-seven patients with available diagnostic biopsy specimens were identified from a previously reported post-RP validation study of Decipher in a cohort of 169 patients treated at Cleveland Clinic. The core with at least 1mm tumor of the highest Gleason grade was sampled and subjected to whole transcriptome analysis. Decipher was calculated based on a locked random forest model. Cox multivariable (MVA) proportional hazards model and survival c-index were used to evaluate the performance of Decipher. Results: 61% of patients had biopsy Gleason score 6 and 67% of patients had NCCN intermediate risk disease. With a median 8 years follow up, 8 patients metastasized and 3 of these patients died of PCa. Decipher had a c-index of 0.80 (95% confidence interval [CI], 0.58-0.95) compared to 0.58 (95% CI, 0.18-0.91) for biopsy Gleason score and 0.57 (0.57; 95% CI, 0.23-0.89) for preoperative PSA at 10 years post-RP for prediction of metastasis. A combined model consisting of Decipher, preoperative PSA, and Gleason score had a c-index of 0.84 (95% CI, 0.68-0.96). On MVA, Decipher was the only significant predictor of metastasis when adjusting for age, preoperative PSA and biopsy Gleason score (Decipher hazard ratio per 10% increase: 1.72; 95% CI, 1.04–2.83; P = 0.02). Conclusions: Decipher was able to predict metastatic outcome from diagnostic biopsy specimens in a cohort of primarily intermediate risk men treated with RP. This additional genomic information may help identify patients who may not be optimal candidates for active surveillance and better identify appropriate first line therapy for men with intermediate risk disease.