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Baby shampoo is used as an alternative surgical skin preparation, but the evidence supporting its use is scarce with no descriptions of efficacy in the periocular region. The authors compare the efficacy of baby shampoo, povidone-iodine (PI, Betadine) and isopropyl alcohol (IA) in reducing eyelid skin bacterial load.Prospective, randomized, comparative, and interventional trial. Bacterial load on adult, human eyelid skin was quantitated before and after cleansing with 1) dilute baby shampoo, 2) 10% PI, or 3) 70% IA. Paired skin swabs were collected from a 1 cm2 area of the upper eyelid of subjects before and after a standardized surgical scrub technique. Samples were cultured on 5% sheep blood agar for 24 hours. The number of colony forming units (CFU) was assessed and bacterial load per square centimeter of eyelid skin was quantified.Baseline and postcleansing samples were assessed from 42 eyelids of 42 subjects (n = 14 for each of baby shampoo, PI, and IA). Before cleansing, similar amounts of bacterial flora were grown from all specimens (median log CFU/cm2 = 2.04 before baby shampoo, 2.01 before PI, 2.11 before IA; p > 0.05). All 3 cleansing agents significantly reduced the bacterial load (p < 0.01 for each). There was no statistically significant difference in postcleansing bacterial load between the 3 cleansing agents (median log CFU/cm2 = 0.48 after baby shampoo, 0.39 after PI, 0.59 after IA; p > 0.05). Change from baseline in bacterial load was statistically similar for all 3 agents (median reduction in log CFU/cm2 = 1.28 with baby shampoo, 1.57 with PI, 1.40 with IA; p > 0.05). These corresponded to bacterial load reductions of 96.3%, 96.6%, and 98.4% for baby shampoo, PI, and IA, respectively.Baby shampoo achieved comparable diminution in eyelid skin bacterial load to PI or IA. These data suggest baby shampoo may be an effective preoperative cleansing agent.