Objectives <p>Symptomatic urinary tract infection (UTI) is a common complication of flexible cystoscopy. Although the European Association of Urology (EAU) and the American Urological Association (AUA) do not recommend routine antibiotic prophylaxis for patients without risk factors, a survey revealed that over 90% of urologists at King Chulalongkorn Memorial Hospital (KCMH) and approximately 60% of Thai urologists routinely prescribe antibiotics for all cystoscopy patients, even those at low risk. This study aimed to examine the necessity of antibiotic prophylaxis following flexible cystoscopy in Thailand.</p> Materials and methods <p>A singlecenter, parallelgroup, randomized controlled noninferiority trial was conducted between August 2024 and January 2025 at the outpatient cystoscopy unit of KCMH, Bangkok, Thailand. A total of 284 patients without UTI risk factors were enrolled and randomly assigned to receive either cefixime or no antibiotics. UTI symptoms were assessed via telephone on day 7 postprocedure. The primary outcome was the incidence of postcystoscopy UTI symptoms, to assess noninferiority compared to those who received antibiotics. The secondary outcome was the overall prevalence of UTI following flexible cystoscopy at KCMH.</p> Results <p>Of the 284 enrolled patients, 265 completed the study. UTI symptoms occurred in 3.85% of the antibiotic prophylaxis group was not inferior to 5.93% of the noantibiotic group. 13 patients (4.9%) with UTI symptoms were successfully managed with oral antibiotics.</p> Conclusions <p>Routine antibiotic prophylaxis after flexible cystoscopy may be omitted in lowrisk patients. These findings support current EAU/AUA guidelines, which do not recommend prophylaxis for uncomplicated cystoscopy.</p> Trial registration <p>TCTR20250402004 on 2 April 2025 (Retrospectively registered).</p>