Purpose To determine the diagnostic accuracy for clinically significant prostate cancer achieved with abbreviated biparametric prostate magnetic resonance (MR) imaging in comparison with full multiparametric contrast material-enhanced prostate MR imaging in men with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (US)-guided biopsy findings; to determine the significant cancer detection rate of biparametric versus full multiparametric contrast-enhanced MR imaging and between-reader agreement for interpretation of biparametric MR imaging. Materials and Methods In this institutional review board-approved retrospective review of prospectively acquired data, men with PSA greater than or equal to 3 ng/mL after negative transrectal US-guided biopsy findings underwent state-of-the-art, full multiparametric contrast-enhanced MR imaging at 3.0-T including high-spatial-resolution structural imaging in several planes, diffusion-weighted imaging at 0, 800, 1000, and 1400 mm2/sec, and dynamic contrast-enhanced MR imaging, obtained without endorectal coil within 34 minutes 19 seconds. One of four radiologists with different levels of expertise (1-9 years) first reviewed only a fraction of the full multiparametric contrast-enhanced MR images, consisting of single-plane (axial) structural imaging (T2-weighted turbo spin-echo and diffusion-weighted imaging), acquired within 8 minutes 45 seconds (referred to as biparametric MR imaging), and established a diagnosis according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2; only thereafter, the remaining full multiparametric contrast-enhanced MR images were read. Men with PI-RADS categories 3-5 underwent MR-guided targeted biopsy. Men with PI-RADS categories 1-2 remained in urologic follow-up for at least 2 years, with rebiopsy (transrectal US-guided or transperineal saturation) where appropriate. McNemar test was used to compare diagnostic accuracies. To investigate between-reader agreement, biparametric MR images of 100 patients were read independently by all three radiologists. Results A total of 542 men, aged 64.8 years ± 8.2 (median PSA, 7 ng/mL), were included. Biparametric MR imaging helped detect clinically significant prostate cancer in 138 men. Full multiparametric contrast-enhanced MR imaging allowed detection of one additional clinically significant prostate cancer (a stage pT2a, intermediate-risk cancer with a Gleason score of 3+4) and caused 11 additional false-positive diagnoses. Diagnostic accuracy for detection of clinically significant cancer of biparametric MR imaging (89.1%, 483 of 542) was similar to that of full multiparametric contrast-enhanced MR imaging (87.2%, 473 of 542). Between-reader agreement of biparametric MR imaging interpretation was substantial (κ = 0.81). Conclusion Biparametric MR imaging allows detection of clinically significant prostate cancer missed by transrectal US-guided biopsy. Biparametric prostate MR imaging takes less than 9 minutes examination time, works without contrast agent injection, and offers a diagnostic accuracy and cancer detection rate that are equivalent to those of conventional full multiparametric contrast-enhanced MR imaging protocols. © RSNA, 2017.