INTRODUCTION: This study aimed to assess post-biopsy infectious complications in patients undergoing who underwent transrectal ultrasound-guided prostate biopsy (TRUS-Bx) with and without transrectal povidone-iodine application by rectal mucosa cleansing. METHODS: A retrospective review of 118 patients at Mersin University Hospital (September 2022 to September 2023) who underwent TRUS-Bx was conducted. Biopsy indications included abnormal digital rectal exam (DRE) findings with any prostate-specific antigen (PSA) and/or PSA > 4 ng/ml. Patient demographics, comorbidities, PSA levels, prostate volumes, pathology results, D'Amico risk score, and infectious complications were analyzed. All patients received prophylactic cefpodoxime (200 mg orally, twice daily) for five days, starting the day before the procedure. Group 1 (48.3%) received cefpodoxime alone, while Group 2 (51.7%) received both cefpodoxime and transrectal povidone-iodine (50 cc, 15 minutes before the procedure). Hospitalizations post-procedure were noted, with a focus on infectious complication rates. RESULTS: A significant post-procedure increase in white blood cell counts was observed overall (p = 0.004). Within the groups, Group 2 showed a statistically insignificant increase (p = 0.307), while Group 1 exhibited a significant increase (p = 0.003). Leukocyte counts and C-reactive protein values increased significantly after TRUS-Bx, with Group 1 experiencing a substantial increase in leukocyte counts and C-reactive protein levels (p < 0.05). No significant differences existed between the groups in terms of demographics, comorbidities, PSA levels, prostate volumes, pathology results, D'Amico risk score, and cancer detection rates. CONCLUSIONS: In addition to antibiotic prophylaxis, transrectal povidone-iodine application effectively reduced post-biopsy infectious complications. This easily applicable, cost-effective, reliable, and well-tolerated method is recommended for all prostate biopsy procedures.