Background: Prostate cancer (PC) patients and providers have tremendous uncertainty as they decide on intervention with adjuvant or salvage radiation therapy (ART, SRT) after radical prostatectomy (RP). We prospectively evaluated the impact of Decipher test, a genomic classifier which predicts metastasis post-RP, on providers’ decision-making for ART and SRT. Methods: 150 men considering ART and 115 men considering SRT from 19 sites across the US were enrolled. Participating providers submitted a management recommendation prior to processing the Decipher test and again after receiving test results. We then followed patients for 12 months to assess actual treatment received and patient reported decisional conflict scale (DCS) and a validated survey on PC-related anxiety. Results: Pre-Decipher, observation was recommended for 89% of adjuvant men and 58% of salvage men. Post-Decipher, 17% of treatment recommendations changed in the adjuvant arm and 30% of recommendations changed in the salvage arm. Among adjuvant men, 78% maintained their recommended management 12 months after Decipher; 76% of salvage men maintained their recommended treatment after Decipher. Among 21 adjuvant men who intensified their treatment (observation to ART or ART to ART plus androgen deprivation therapy), 5 (24%) experienced biochemical recurrence with detectable PSA. In adjuvant men, PC-specific anxiety decreased differently among Decipher risk categories (p-value = 0.045), most notably among Decipher high risk men (9.07 [7.87, 10.26] pre-Decipher, 5.61 [5.35,5.88] 12 months post-Decipher). In salvage men, PC-specific anxiety decreased differently among those whose treatment were concordant (10.28 [8.1,12.47] pre-Decipher, 7.18 [6.82,7.54] 12 months post-Decipher) and those whose treatment were intensified (p-value = 0.01), and decreased differently among low-risk and high-risk Decipher patients (p = 0.04). Conclusions: Use of the Decipher test changed treatment decisions that was consistent with the eventual treatment received in three-fourths of adjuvant and salvage men after RP. Several men that pursued ART experienced PSA progression. PC-specific anxiety decreased in both adjuvant and salvage men. Clinical trial information: NCT02080689