Background: Magnetic resonance imaging (MRI)-ultrasound (US) fusion prostate biopsy has been shown to be able to detect prostate cancer, with the goal of targeting specific lesions. Our objective was to evaluate the ability of this technique to accurately determine the final pathological outcome at the time of radical prostatectomy as compared to standard template 12-core transrectal ultrasound (TRUS) guided prostate biopsy. Methods: We performed a retrospective analysis of patients who underwent both prostate biopsy and prostatectomy at the Cleveland Clinic. Patients who underwent standard template 12-core TRUS biopsies between January 2005 through December 2013, and MRI-US fusion biopsies from January 2014 through June 2015 were included. Patients who had more than 12 cores taken during TRUS biopsy were excluded. Relevant covariates included patient demographics as well as pre-biopsy PSA and prostate size, which were collected from the electronic medical record. Continuous variables were compared using Wilcoxon rank-sum tests and categorical variables were assessed with χ2 test. Results: In total 543 patients were included. Of these, 491 underwent 12-core standard template TRUS biopsy whereas 54 underwent MRI-US fusion biopsy. Between the two groups there were no significant differences in age (median 62 years versus 63 years, p = 0.21), race (17.5% versus 12.3 % African American, p = 0.32), family history (31.5% versus 29.3% positive, p = 0.74), prostate size (47.75g, IQR 39.5-59 versus 42.7g, IQR 37-56, p = 0.08), pre-biopsy PSA (5.2 ng/mL, IQR 4.1-7.6 versus 4.97, IQR 3.24-6.95, p = 0.14). Of the fusion biopsy patients, 14 of 54 (25.9%) were upgraded from biopsy to prostatectomy, whereas 214 of 491 (43.6%) of TRUS biopsy patients were upgraded (p = 0.02). Conclusions: Of men undergoing transrectal biopsy for the diagnosis of prostate cancer, MRI-US fusion techniques have a lower rate of upgrading at final pathology at prostatectomy as compared to standard 12-core TRUS-guided biopsy.