Background Multiparametric prostate MRI (mpMRI) is being increasingly adopted for work-up of prostate cancer. For patients selected to omit biopsy, we identified factors associated with repeat MRI, eventual prostate biopsy, and subsequent detection of clinically significant prostate cancer (csPCa, Grade Group ≥ 2).Methods We identified biopsy-naïve men presenting with PSA 2–20 ng/mL (March 2018-June 2021) undergoing initial mpMRI with PIRADS 1–3 lesions who were not selected for biopsy with ≥ 6 months follow-up. We examined factors associated with repeat mpMRI, progression to biopsy, and subsequent detection of csPCa with univariable and multivariable logistic regression.Results Of 1494 men, 31% (463/1494) did not pursue biopsy. PSA density (PSAD) ≤ 0.1, prostate health index (PHI) < 55, and PIRADS 1–2 were associated with omission of prostate biopsy. csPCa diagnosis-free survival was 97.6% (326/334) with median follow up of 23.1 months (IQR 15.1–34.6 months). Black race, PSA, PHI, PSA density, and PSA and PHI velocity were significant predictors of undergoing repeat mpMRI (15.6%, 52/334) and subsequent biopsy (8.4%, 28/334). 8 men were subsequently diagnosed with csPCa (N = 7 on prostate biopsy; N = 1 incidentally on holmium enucleation of prostate). All patients diagnosed with csPCa had PIRADS 4–5 on repeat mpMRI.Conclusions The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI was low at 2.4%. Decisions to omit biopsy after reassuring PHI and mpMRI appear safe.