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We assessed the risk of significant prostate cancer being detected after low suspicion magnetic resonance imaging or suspicious magnetic resonance imaging with benign magnetic resonance imaging guided biopsies in men with prior negative systematic biopsies.Overall 289 prospectively enrolled men underwent magnetic resonance imaging followed by repeat systematic and targeted biopsies of any suspicious lesions at baseline. A total of 194 patients with low suspicion magnetic resonance imaging or benign target biopsies were suitable for this study. Those who were negative for prostate cancer at baseline were followed for at least 3 years. We calculated the negative predictive values of magnetic resonance imaging in ruling out any prostate cancer and significant prostate cancer, defined as any core with Gleason score greater than 6, or more than 2 positive cores/cancerous core 50% or greater.Prostate cancer was detected in 38 of 194 (20%) patients during the median study period of 47 months (IQR 43–52). The overall negative predictive value of magnetic resonance imaging in ruling out any and significant prostate cancer was 80% (156 of 194) and 95% (184 of 194), respectively. No patient with low suspicion magnetic resonance imaging had intermediate/high grade cancer (Gleason score greater than 6). The majority of patients with no cancer during followup (132 of 156, 85%) had a decreasing prostate specific antigen and could be monitored in primary care.Low suspicion magnetic resonance imaging in men with prior negative systematic biopsies has a high negative predictive value in ruling out longer term, significant cancer. Therefore, immediate repeat biopsies are of limited clinical value and could be avoided even if prostate specific antigen is persistently increased.