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Abstract: Background<br>The hands of the medical staff play an important role in transmission of pathogens in the health care environment. Hand hygiene is efficient, easy to perform and cost-effective. Safety, tolerability and acceptance of hand hygiene preparations play a major role in hand hygiene compliance, and apply, in particular, to formulations with high anti-viral activity.<br><br>Aim<br>Clinical trial to evaluate the safety and tolerability of different virucidal hand rubs.<br><br>Methods<br>In a randomized, double-blind, four-period cross-over trial, healthy volunteers received three different virucidal hand rubs (P1-P3) and a reference product (R) in randomized sequence over a period of 4 days each with a washout period. The primary endpoint was skin barrier function measured by transepidermal water loss (TEWL) after application.<br><br>Results<br>Twenty-two subjects (seven male, 15 female; median age 25, range 21-54) were randomized and started at least one period. TEWL was 22.5; 95 %-confidence interval (CI): 19.6-25.4 after P1, 16.3; 13.5-19.1 after P2, 16.4; 13.4-19.3 after P3, and 24.0; 21.1-27.0 after R; p 0.0001. The percentage of subjects experiencing at least one adverse event (AE) was 86 % with P1, 25 % with P2, 89 % with P3 and 56 % with R. The majority of AEs were skin reactions classified as of mild severity. No serious AEs were observed.brbrConclusions