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To assess the complications of transrectal (TR) compared to transperineal prostate (TP) biopsies.Men diagnosed with prostate cancer between 1 April 2014 and 31 March 2017 in England were identified in the National Prostate Cancer Audit. Administrative hospital data were then used to categorize the type of prostate biopsy and subsequent complications requiring hospital admission. Administrative hospital data were used to identify patients staying overnight immediately after biopsy and those readmitted separately for hospital admissions because of sepsis, urinary retention or haematuria. Procedure-related mortality and total length of hospital stay within 30 days were also recorded. Generalized linear models were used to calculate adjusted risk differences (aRDs).A total of 73 630 patients undergoing prostate biopsy were identified. Those undergoing TP biopsy (n = 13 723) were more likely to have an overnight hospital stay (12.3% vs 2.4%; aRD 9.7%, 95% confidence interval [CI] 7.1-12.3), were less likely to be readmitted because of sepsis (1.0% vs 1.4%; aRD -0.4%, CI -0.6 to -0.2), and were more likely to be readmitted with urinary retention (1.9% vs 1.0%; aRD 1.1%, CI 0.7-1.4) than those undergoing a TR biopsy (n = 59 907). There were no significant differences in the risk of haematuria or mortality.Our results showed that TP biopsy had a lower risk of readmission for sepsis but a higher risk of readmission for urinary retention than TR biopsy. Use of the TP route would prevent one readmission for sepsis in 278 patients at the cost of three additional patients readmitted for urinary retention.