This article reviews the results and conclusions from four pivotal and two comparative clinical trials. The six randomized, controlled, single-blinded, parallel-group clinical trials were conducted to determine which antiseptic is best for use as a patient preoperative skin preparation. The objective of these studies was to compare the immediate, persistent (residual), and cumulative antimicrobial efficacy and safety of 2% chlorhexidine gluconate (CHG) combined with 70% isopropyl alcohol (IPA) (ChloraPrep); another combination CHG and IPA antiseptic (CHG+IPA) and 2% aqueous CHG alone; 4% CHG (Hibiclens) alone; 70% isopropyl alcohol (IPA) alone; and an iodine-containing solution, 10% povidone-iodine (Betadine) alone as preoperative skin topical antiseptics for potential prevention of nosocomial infections.