Background: Contamination of the surgical site by vaginal flora may lead to surgical site infection (SSI) after hysterectomy. While vaginal preparation to reduce this risk is standard, there is conflicting evidence regarding the appropriate choice of preparation.

Objective: The aim of this study was to assess whether a large-scale transition of vaginal antisepsis prior to hysterectomy from povidone iodine (PI) to 4% aqueous chlorhexidine gluconate (CHG) across multiple sites would improve SSI rates.

Methods: This was a prospective, multi-center, observational quality improvement (QI) study performed at six sites. Each site collected risk-adjusted SSI rates based on NSQIP smoothed rates models for one year prior and two years following large-scale transition to CHG for vaginal antisepsis. Results: The average pre-intervention SSI rate was 4.09%, and post-intervention rate was 3.88% with individual sites reporting rates ranging from 2.19% to 5.13%. Four out of six participating sites demonstrated trends of lower SSI rates.

Conclusion: CHG may contribute to reductions in the incidence of surgical site infections, and vaginal antisepsis with CHG should be considered within an institution’s efforts to reduce surgical site infections after hysterectomy.