For this study, researchers analyzed whether patients with specified comorbidities who had simple cystourethroscopy had lower post-procedural infection (urinary tract infection or sepsis) rates when antimicrobial prophylaxis was administered. By using Epic® reporting software, they analyzed all simple cystourethroscopy operations carried out by their urology department’s doctors between August 4, 2014, and December 31, 2019. The incidence of post-procedural infection, the use of antibiotic prophylaxis, and the presence of co-morbidities were all recorded. Mixed effects logistic regression models were used to quantify the impact of antimicrobial prophylaxis and patient comorbidities on the likelihood of post-procedural infection. To prevent infection, antimicrobials were administered before 7,001 out of 8,997 cystourethroscopies. Total post-operative infections amounted to 83 (0.9%). Antimicrobial prophylaxis was associated with a significantly reduced risk of infection in the postoperative period compared to no prophylaxis (OR 0.51, 95% CI 0.35-0.76; P<0.01). Antimicrobial prophylaxis had a 100-to-1 odds ratio of preventing post-procedural infection. Antimicrobial prophylaxis for post-procedural infection prevention was not significantly helpful for any examined comorbidities. The incidence of infection following a cystourethroscopy performed in a doctor’s office was only 0.9%. Despite antimicrobial prophylaxis’s ability to reduce the overall risk of post-procedural infection, many patients would have to be treated for this effect (100). In none of the comorbidity groups we studied, antibiotic prophylaxis appreciably lowers the incidence of post-procedural infection. These results indicate that antibiotic prophylaxis during uncomplicated cystourethroscopy should not be recommended based on the co-morbidities assessed in this study.