Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 18 5 2026 10 05 677 684 Farah Farzaneh Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Nikpour Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Farshad Abedi-Kebria Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran Shaghayegh Hooshmand Chayijan Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zahra Bakhtiyari Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Amir Soltani Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2026 04 28 2026 08 14 Background and Objectives: Surgical site infection (SSI) is an important complication following hysterectomy. Given the rising antimicrobial resistance in Iran, this multi-year cohort study aimed to identify independent predictors of SSI after hysterectomy. Materials and Methods: This retrospective cohort study included patients undergoing total abdominal hysterectomy (2019-2024). Independent risk factors were identified via multivariable binary logistic regression. Model performance was validated using receiver operating characteristic (ROC) curve analysis. Continuous variable cut-off points were determined using the Youden index. Results: Among 690 patients, the SSI rate was 5.2%. Multivariable analysis identified obesity (BMI ≥ 30 kg/m²) (Adjusted Odds Ratio [aOR]: 4.11; 95% CI: 1.81–9.32; p < 0.001) and operative duration (aOR: 1.02 per minute; p < 0.001) as the strongest independent predictors. ROC analysis demonstrated excellent discrimination (AUC = 0.88). Infection risk increased critically when surgery exceeded 180 minutes or in obese patients. Preoperative non-standard antibiotic prophylaxis consisting solely of clindamycin was associated with a 7.5-fold increased SSI risk (P=.006). Microbiological analysis revealed a 30.6% prevalence of multidrug-resistant and ESBL-producing bacteria. Conclusion: Obesity and prolonged operative time are independent predictors of SSI. We recommend weight-based dosing, strict intraoperative re-dosing during prolonged procedures, and mandatory antimicrobial stewardship to mitigate risks associated with non-standard prophylaxis. https://ijm.tums.ac.ir/index.php/ijm/article/view/6155 https://ijm.tums.ac.ir/index.php/ijm/article/download/6155/1928