Enhanced histological detection of clinically significant prostate cancer is the goal of the prebiopsy imaging pathway. Risk stratification at a prebiopsy meeting can facilitate optimization of lesion targeting. We aimed to evaluate the feasibility of cognitive registration, freehand transperineal prostate biopsy in a biopsy-naïve population following biparametric MRI for the detection of clinically significant disease (International Society of Urological Pathology Grade Group ≥2). A consecutive series of biopsy-naïve men, prospectively recorded between July 2018 and March 2023, were risk-stratified at our prebiopsy meeting following biparametric MRI to undergo either target-only biopsy or target with systematic biopsy. Biopsies were routinely performed under local anesthesia and without antibiotic prophylaxis in the outpatient setting. Overall prostate cancer and clinically significant prostate cancer detection were primary outcomes. Of 1251 biopsies, prostate cancer was detected in 84% and clinically significant disease in 70.6%. Prostate cancer and clinically significant disease were detected in 86.2% and 76.5% of target-only biopsies, respectively, and in 78.7% and 56.3% of target with systematic biopsies. Postbiopsy complication rate was 0.7%. Prebiopsy biparametric MRI with risk stratification at a prebiopsy meeting in the setting of cognitive targeting and freehand transperineal prostate biopsy yielded a high detection of prostate cancer that is comparable to other studies. These data support the use of cognitive registration, freehand transperineal prostate biopsy as safe, feasible, and cost-effective.