ChloraPrep (2% chlorhexidine gluconate + 70% isopropyl alcohol [CHG + IPA] in a 3.0-mL applicator) is a recently approved antiseptic for preoperative skin preparation. This controlled open-label trial assessed the immediate and persistent antimicrobial efficacy and safety of CHG + IPA compared with 70% IPA or a 2% CHG aqueous solution alone. Each antiseptic significantly reduced abdominal and inguinal microbial counts from baseline at 10 minutes, 6 hours, and 24 hours (P =.0001). CHG + IPA provided significantly more persistent antimicrobial activity on abdominal sites than IPA (P =.003) or CHG (P =.028) at 24 hours. No skin irritations were reported for any of the three antiseptics.