BACKGROUND AND OBJECTIVE: A local anaesthetic ultrasound-guided transperineal (LATP) prostate biopsy has advantages over transrectal ultrasound (TRUS)-guided biopsy, with improved magnetic resonance imaging (MRI)-guided prostate cancer detection and lower rates of infection-related complications. However, uncertainty remains regarding the cost effectiveness of an LATP biopsy compared with a TRUS biopsy. METHODS: Between December 2021 and September 2023, the TRANSLATE randomised clinical trial allocated 1126 men to receive either a TRUS (n = 564) or an LATP (n = 562) biopsy at ten sites in the UK. All men were biopsy naïve and underwent prebiopsy MRI. Participants were followed up for 4 mo after a biopsy. The economic analysis is a within-trial analysis at 4 mo after biopsy, conducted from a National Health Service perspective. We assessed resource use, health care costs, and quality-adjusted life years (QALYs) across 4 mo of follow-up from an intention-to-treat perspective. We addressed missing data using multiple imputation. Incremental cost-effectiveness ratios were calculated, with uncertainty characterised using nonparametric bootstrapping. The TRANSLATE trial is registered at ISRCTN (ISRCTN98159689) and is complete. KEY FINDINGS AND LIMITATIONS: The total mean costs over the 4 mo of follow-up were £1062 in the LATP arm and £917 in the TRUS arm (adjusted mean difference £149; 95% confidence interval [CI] £61-236, p = 0.001). The total mean QALYs at 4 mo were 0.282 in the LATP arm and 0.284 in the TRUS arm (adjusted mean difference -0.004; 95% CI -0.009 to 0.001, p = 0.098). CONCLUSIONS AND CLINICAL IMPLICATIONS: An LATP biopsy has a higher mean cost, and no significant difference in mean QALYs, compared with a TRUS biopsy at 4 mo after the procedure. A time of 4 mo is too soon to reflect any impact from the 5.7% diagnostic uplift for LATP versus TRUS biopsy on the detection of intermediate-/high-grade prostate cancer seen in the TRANSLATE trial. A further analysis beyond this period is needed to fully interpret the cost-effectiveness results.