OBJECTIVE: To compare healthcare workers' skin tolerance for and acceptance of 3 alcohol-based hand rub formulations. DESIGN: Double-blind, randomized, crossover clinical trial. SETTING: Intensive care unit in a university hospital. PARTICIPANTS: Thirty-eight healthcare workers (HCWs). INTERVENTION: A total of 3 alcohol-based hand rub formulations (hereafter, formulations A, B, and C) were used in random order for 3-5 consecutive working days during regular nursing shifts. Formulations A and B contained the same emollient, and formulations B and C contained the same alcohol at the same concentration. Use of each test formulation was separated by a "washout" period of at least 2 days. A visual assessment of skin integrity by a blinded observer using a standard 6-item scale was conducted before and after the use of each formulation. Univariate and multivariate analyses were used for the assessment of risk factors for skin alteration, and product acceptability was assessed by use of a customized questionnaire after the use of each formulation. RESULTS: Thirty-eight HCWs used each of 3 formulations for a median of 3 days (range, 3-5 days). The mean amount of product used daily (+/-SD) was 54.9+/-23.5 mL (median, 50.9 mL). Both subjective and objective evaluation of skin conditions after use showed lower HCW tolerance for product C. Male sex (odds ratio [OR], 3.17 [95% confidence interval {CI}, 1.1-8.8]), fair or very fair skin (OR, 3.01 [95% CI, 1.1-7.9]), skin alteration before hand rub use (OR, 3.73 [95% CI, 1.7-8.1]), and use of formulation C (OR, 8.79 [95% CI, 2.7-28.4]) were independently associated with skin alteration. CONCLUSIONS: This protocol permits a fast-track comparison of HCWs' skin tolerance for different alcohol-based hand rub formulations that are used in healthcare settings. The emollient in formulation C may account for its inferior performance.