ObjectiveTo assess the outcomes of pre‐biopsy magnetic resonance imaging (MRI) pathways, as a tool in biopsy‐naïve men with suspicion of prostate cancer, in routine clinical practice. Secondary outcomes included a comparison of transrectal MRI‐directed biopsy (TR‐MRDB) and transperineal (TP)‐MRDB in men with suspicious MRI.Patients and MethodsWe retrospectively assessed a two‐centre cohort of consecutive biopsy‐naïve men with suspicion of prostate cancer who underwent a Prostate Imaging‐Reporting and Data System version 2 (PI‐RADS v2) compliant pre‐biopsy MRI in a single, high‐volume centre between 2015 and 2019 (Centre 1). Men with suspicious MRI scans underwent TR‐MRDB in Centre 1 and TP‐MRDB with additional random biopsies (RB) in Centre 2. The MRI and histopathology were assessed in the same institution (Centre 1). Outcomes included: (i) overall detection rates of Grade Group (GG) 1, GG ≥2, and GG ≥3 cancer in men with suspicious MRI; (ii) Biopsy‐avoidance due to non‐suspicious MRI; and (iii) Cancer detection rates and biopsy‐related complications between TR‐ and TP‐MRDB. To reduce confounding bias for MRDB comparisons, inverse probability weighting (IPW) was performed for age, digital rectal examination, prostate‐specific antigen (PSA), prostate volume, PSA density, and PI‐RADS category.ResultsOf the 2597 men included, the overall GG 1, GG ≥2, and GG ≥3 prevalence was 8% (210/2597), 27% (697/2597), and 15% (396/2597), respectively. Biopsy was avoided in 57% (1488/2597) of men. After IPW, the GG 1, GG ≥2 and GG ≥3 detection rates after TR‐ and TP‐MRDB were comparable at 24%, 57%, and 32%; and 18%, 64%, and 38%, respectively; with mean differences of −5.7% (95% confidence interval [CI] −13% to 1.4%), 6.1% (95% CI −2.1% to 14%), and 5.7% (95% CI −1.7% to 13%). Complications were similar in TR‐MRDB (0.50%) and TP‐MRDB with RB (0.62%; mean difference 0.11%, 95% CI −0.87% to 1.1%).ConclusionThis high‐volume, two‐centre study shows pre‐biopsy MRI as a decision tool is implementable in daily clinical practice. Compared to recent trials, a substantially higher biopsy avoidance rate was achieved without compromising GG ≥2/GG ≥3 detection and coinciding with lower over detection rates of GG 1 cancer. Prostate cancer detection and complication rates were comparable for TR‐ and TP‐MRDB.