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Objective: It is unknown how risk factors for infection after transrectal prostate biopsy interact. We designed a study to evaluate this. Methods: We identified biopsy procedures from 2006 to 2020 in the Swedish nationwide database PCBaSe. Primary outcome was post-biopsy infection, defined as a dispensed prescription ofa urinary tract antibiotic and secondary outcome was inpatient care for infection both within 30 days. Riskfactors were age, diabetes, medical treatment of lower urinary tract symptoms (LUTSs), prostate enlargement, immunosuppressives, corticosteroids, and defined antibiotic exposure during the past 1-12 months. When analysing risk in men with several risk factors clinically related factors were grouped as urinary tract infection (UTI)-antibiotics, treatment of LUTS, immunosuppressives including corticosteroids, and diabetes. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI). Results: A total of 139,056 transrectal prostate biopsy procedures were analysed. The grouped risk factors were significantly associated with post-biopsy infection (multivariable ORs: 1.22-1.72). Infection increased with number of risk factors; none: 4.0% (95% CI: 3.8-4.1), one: 6% (95% CI: 5.9-6.4), two: 10% (95% CI: 9.3-11), and three or four: 12% (95% CI: 9.8-14); inpatient care increased from 2.0% (95% CI: 1.9-2.1) to 3.1% (95% CI: 2.2-4.4). Conclusion: Infection risk after transrectal prostate biopsy incrementally increases with the number of risk factors. Clinical Implications: The transrectal biopsy route should be used with caution for patients with several risk factors for post-biopsy infections. Patient Summary: Diabetes, urinary symptoms, previous urinary infection, and immune suppressing medication increase the risk of infection after a prostate biopsy through the rectum. Patients with many of these conditions have a particularly high risk. What does the study add? We used nationwide register data to estimate the infection risk after transrectal prostate biopsy by the number of these risk factors: diabetes, medical treatment of lower urinary tract symptoms, immunosuppressives including corticosteroids, and use of urinary tract antibiotics the past year. The risk incrementally increased from 4.0% in men with no risk factor to 12% in those with 3 or 4. Take Home Message: Infection after transrectal prostate biopsy increases with number of risk factors: diabetes, medical treatment of lower urinary tract symptoms, immunosuppressives including corticosteroids, and use of urinary tract antibiotics the past year, from 4.0% (none) to 12% (3 or 4).