Many surgeons request use of 10% povidone-iodine (PI) for vaginal antisepsis; however, when PI is contraindicated, some surgeons request use of chlorhexidine gluconate (CHG) instead. The purpose of this randomized controlled trial was to determine any significant differences in self-reported symptoms associated with vaginal antisepsis with either 10% PI scrub or 4% CHG with 4% isopropyl alcohol. The control group comprised 62 participants who underwent vaginal antisepsis with the PI product, and the intervention group comprised 58 participants who underwent vaginal antisepsis with the CHG product. Participants completed surveys immediately before surgery, immediately after surgery, and 48 to 72 hours after surgery. No significant differences were found in the reported vaginal symptoms between the two groups for any survey. One participant in the intervention group reported symptoms consistent with an allergic reaction. Additional studies are needed on the use of CHG for vaginal antisepsis.