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We compared handwashing (HW) and alcohol-based handrub (ABH) for skin tolerance, acceptability, and hand hygiene compliance in health-care workers (HCWs) in a multicentric study.Before/after study over two periods (P1 and P2) in seven ICUs. Monitoring of methicillin-resistant Staphylococcus aureus (MRSA) acquisition in two ICUs (U4 and U6).All HCWs of the seven ICUs, and the patients of U4 and U6 without MRSA carriage on admission.Handwashing was available in P1 and P2. ABH was introduced after P1 and available throughout P2. HCWs completed questionnaires on skin tolerance in P1 and P2, and on acceptability in P2. Compliance with hand hygiene was assessed in P1 and P2 using a standardized method. ICU-acquired MRSA colonization/infection in U4 and U6 was recorded.Hand erythema was reported during P1 and P2 by 21.7 and 11% of HCWs, respectively (P = 0.01), itching by 15.8 and 7.1% (P = 0.02), oozing by 0.8 and 1.1% (P = 0.82), and bleeding by 4.2 and 1.1% (P = 0.1). ABH was considered easier and quicker than HW (P < 0.01), but overall acceptability did not differ between the two. Compliance increased from 51% (334/647) in P1 to 60% (251/418) in P2, P < 0.01. No significant reduction in MRSA colonization/infection between P1 and P2 (P = 0.30) was observed, but the study was underpowered.Self-report questionnaires show that when ABH is available in ICUs, fewer unpleasant skin sensations are reported. ABH is considered to be easier and quicker to use than HW and compliance is improved after glove removal.