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OBJECTIVES To describe the detection rate of (clinically significant) prostate cancer (csPCa) in a large cohort of patients who underwent transperineal ultrasound guided systematic prostate biopsy using a probe-mounted transperineal access system with Magnetic Resonance Imaging (MRI) cognitive fusion in case of a PIRADS 3-5 lesion (TPB-US) under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure related complications with a cohort of patients undergoing transrectal ultrasound guided biopsies (TRB-US) and transrectal MRI guided biopsies (TRB-MRI). PATIENTS AND METHODS This is an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen (PSA) -level, clinical tumour stage, prostate volume, MRI-parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure related complications were assessed. CsPCa was defined as ISUP≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection (UTI). RESULTS A total of 1,288 TPB-US procedures were evaluated. The overall detection rate for prostate cancer in biopsy naive patients was 73%, and for csPCa 63%. The incidence of hospitalization was 1% in TPB-US (13/1,288), compared to 4% in TRB-US (8/214) and 3% TRB-MRI (7/219) (p=0.002). CONCLUSIONS Contemporary combined systematic and target transperineal prostate biopsy under ultrasound-guidance with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure related complications.