Background: A 17 gene panel (Oncotype Dx Genomic Prostate Score, GPS) has been validated as an independent predictor of adverse pathology (AP, defined as pathological GS 4+3 or higher and/or pT3+) in men treated with radical prostatectomy (RP) for prostate cancer (PCa). Multiparametric Magnetic Resonance Imaging (mpMRI) may help guide prostate biopsies. We explored synergies between GPS and mpMRI to aid in PCa management decisions. Methods: A cohort of men with NCCN Low and Intermediate-Risk PCa who were managed with RP was identified from a clinical database. Patients were required to have had a simultaneous mpMRI-guided and systematic biopsy and to have undergone RP within 6 months. Biopsy tissue of the highest Gleason pattern was used for calculation of GPS. The primary endpoint was AP. Secondary endpoints included the range of GPS within UCLA prostate MRI risk groups and median GPS when there was discrepancy between MRI and systematic biopsy Gleason Score (GS). Logistic regression models were fit to evaluate the relationship between GPS (per 20 units) and AP. Results: 134 men met criteria for the primary endpoint. Median age was 62 years (range 46-77). NCCN Low & Intermediate-Risk PCa was present in 16%, and 84% of men, respectively. Biopsy GS 3+3/3+4/4+3 was present in 19%, 67%, and 13%, respectively. In a univariable model, GPS was associated with AP (OR 3.8, 95% CI 2.1 to 7.4, p < 0.001). After adjustment for highest biopsy GS and clinical T-stage, GPS remained significantly associated with AP (OR 3.4, 95% CI 1.8 to 6.8, p = 0.0004). A wide and overlapping distribution of GPS was noted across UCLA MRI prostate risk groups, indicating that GPS provides information that is distinct from what can be determined from mpMRI. When there was a discrepancy between mpMRI and systematic biopsy GS, mpMRI targeted lesions with higher GS had higher median GPS (33, range 13-70) than systematic biopsies with higher GS (median GPS 25, range 15-55). Conclusions: GPS provides independent and complementary prognostic information to mpMRI-guided biopsies. The combination of mpMRI for biopsy guidance and GPS for molecular analysis may optimize prediction of AP and improve patient selection for treatment versus surveillance.