BackgroundThe long‐term prevalence of clinically significant prostate cancer (csPCa) in patients with initial negative prostate biopsy is unknown.PurposeTo investigate the rate of csPCa of men with initial negative biopsy.Study TypeRetrospective analysis of prospectively collected data.PopulationA total of 197 men (mean age 63 years [SD ±6.98, range 29–79]) without csPCa on initial biopsy and available baseline biparametric prostate MRI (bpMRI).Field Strength/Sequence3.0 T, turbo spin‐echo T2‐weighted (axial and sagittal) and three sets of diffusion‐weighted imaging using single‐shot spin‐echo planar imaging (5 b‐values 0–500 seconds/mm2; 2 b‐values 0 and 1500 seconds/mm2, and 2 b‐values 0 and 2000 seconds/mm2).AssessmentBpMRI was read using Prostate Imaging Reporting Data System (PI‐RADS) v2.1. Systematic or targeted biopsy results served as reference standard.Statistical TestsContinuous variables were compared using Kruskal–Wallis rank sum test. Categorical variables were compared using either Fisher's exact test or Pearson's chi‐square test. Uni‐ and multivariate regression odds ratios (95% confidence interval) were used to study factors affecting csPCa being diagnosed during follow‐up. Time to diagnosis of csPCa is calculated using the Kaplan–Meier method.ResultsOf 197 men, 74 (38%), 57 (29%), and 66 (34%) presented with PI‐RADS 1–2, 3, and 4–5 findings in the baseline bpMRI. During the median follow‐up of 52 months, 8.1%, 5.3%, and 18.2% of these men were diagnosed with csPCa, respectively. Baseline PI‐RADS finding was the only factor that associated with csPCa found during the follow‐up.Data ConclusionBaseline bpMRI with PI‐RADS scores 1–3 and initial biopsies negative of csPCa had low rate of csPCa during follow‐up, which supports more conservative follow‐up for them but further research with longer follow‐up is warranted.Level of Evidence3Technical EfficacyStage 2