OBJECTIVES: Primary objectives: To determine whether local anesthetic transperineal (LATP) prostate biopsy improves the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) Grade Group ≥2 disease (i.e. any Gleason pattern 4 disease), compared to transrectal ultrasound-guided (TRUS) prostate biopsy, in biopsy-naïve men undergoing biopsy based on suspicion of csPCa. SECONDARY OBJECTIVES: To compare i) infection rates, ii) health-related quality of life (HRQoL), iii) patient-reported procedure tolerability, iv) patient-reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), v) number of subsequent prostate biopsy procedures required, vi) cost-effectiveness, vii) other histological parameters, and viii) burden and rate of detection of clinically insignificant PCa (ciPCa) (ISUP Grade Group 1 disease) in men undergoing these two types of prostate biopsy. PATIENTS AND METHODS: The TRANSLATE trial is a UK-wide, multi-centre, randomised clinical trial that meets the criteria for level-one evidence in diagnostic test evaluation. TRANSLATE is investigating whether LATP biopsy leads to a higher rate of detection of csPCa compared to TRUS prostate biopsy. Both biopsies are being performed with an average of 12 systematic cores in 6 sectors (depending on prostate size), plus 3-5 target cores per multi-parametric/bi-parametric magnetic resonance imaging (mp/bp-MRI) lesion. LATP biopsy is performed using an ultrasound probe-mounted needle guidance device (either the "Precision-Point" or BK UA1232 system). TRUS biopsy is performed according to each hospital's standard practice. The study is 90% powered to detect a 10% difference (LATP biopsy hypothesised at 55% detection rate for csPCa, versus 45% for TRUS biopsy). 1,042 biopsy-naïve men referred with suspected PCa need to be recruited. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of LATP biopsy versus TRUS biopsy in the primary diagnostic setting.