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We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging to diagnose clinically significant prostate cancer and compared it with the diagnostic accuracy of transperineal saturation prostate biopsy.From January 2011 to February 2018 repeat saturation prostate biopsy (the reference test) was done due to suspicion of cancer in 1,032 men with a median age of 63 years in whom median prostate specific antigen was 8.6 ng/ml. All patients underwent 3.0 Tesla pelvic multiparametric magnetic resonance imaging before saturation prostate biopsy. Additional targeted fusion prostate biopsy was done of lesions with a PI-RADS™ (Prostate Imaging Reporting and Data System) score of 3 or greater.T1c prostate cancer was found in 372 of the 1,032 patients (36%). Of these cases 272 (73.1%) were classified as clinically significant prostate cancer. Saturation prostate biopsy vs targeted fusion prostate biopsy and a PI-RADS score of 3 or greater vs targeted fusion prostate biopsy and a PI-RADS score of 4 or greater diagnosed 95.6% vs 83.8% vs 60.3% of clinically significant prostate cancers (p <0.0001). Saturation prostate biopsy missed 12 of 272 clinically significant prostate cancers (4.5%) vs 44 (16.2%) and 108 of 272 (39.7%) missed by targeted fusion prostate biopsy and a PI-RADS score of 3 or greater and a score of 4 or greater, respectively (p <0.0001). As a triage test multiparametric magnetic resonance imaging would have spared 49.3% vs 73.6% of patients using a PI-RADS cutoff of 3 or greater vs 4 or greater.Multiparametric magnetic resonance imaging could significantly reduce the number of unnecessary repeat prostate biopsies in about 50% of cases in which a PI-RADS score of 3 or greater is used. At the same time patients should be informed of the 16.2% and 39.7% false-negative rates of clinically significant prostate cancer for targeted fusion prostate biopsy of PI-RADS 3 or greater and 4 or greater lesions, respectively.