Purpose To measure the precision in placement of a biopsy needle in a magnetic resonance (MR) imaging-detected target with transrectal ultrasonography (US), to document the clinical relevance of precision, and to report on the precision of cognitive and software-based registrations. Materials and Methods This prospective study was approved by the institutional review board and performed between June 2013 and September 2013. Patients provided informed verbal consent. Two cores each were obtained with cognitive and fusion techniques in 88 patients with a Prostate Imaging Reporting and Data System version 1 score of at least 3. Precision was measured with Euclidian geometry by using the Digital Imaging and Communications in Medicine archives of the biopsy as the distance from the core to the center (dCC) and the distance from the core to the surface of the target modeled as a sphere. To address clustering of data from multiple cores in the same patients, analyses of precision focused on the best shot for a patient or a technique. The Welch unequal variance t test and Yates corrected χ2 test were used as appropriate. Results Mean precision was 2.5 mm (95% confidence interval: 1.8 mm, 3.3 mm). Positive cores were closer to the center than were negative cores (dCC: 1.7 mm vs 3.1 mm, respectively; P = .025). More cancers were detected with on-target than off-target cores (33 of 71 cores [46.5%] vs three of 17 cores [17.6%]; P = .03). Cores obtained with the fusion technique achieved a higher precision than did cores obtained with the cognitive technique (dCC: 2.8 mm vs 7.1 mm, respectively; P < .0001). Targeted cores demonstrated cancer in 44 patients. Fewer cancers were detected with the cognitive technique than with the fusion technique (31 of 44 patients [70.5%] vs 40 of 44 patients [90.9%]; P = .03). Conclusion A deformable MR imaging/transrectal US image registration system achieved a higher precision and depicted cancer in more patients than did the cognitive freehand technique. © RSNA, 2018.