INTRODUCTION: Hand hygiene is one of the cornerstones of the prevention of health care-associated infection, but health care worker (HCW) compliance with good practices remains low. Alcohol-based handrub is the new standard for hand hygiene action worldwide and usually requires a system change for its successful introduction in routine care. Product acceptability by HCWs is a crucial step in this process. METHODS: We conducted a prospective intervention study to compare the impact on HCW compliance of a liquid (study phase I) versus a gel (phase II) handrub formulation of the same product during daily patient care. All staff (102 HCWs) of the medical intensive care unit participated. Compliance with hand hygiene was monitored by a single observer. Skin tolerance and product acceptability were assessed using subjective and objective scoring systems, self-report questionnaires, and biometric measurements. Logistic regression was used to estimate the association between predictors and compliance with the handrub formulation as the main explanatory variable and to adjust for potential risk factors. RESULTS: Overall compliance (phases I and II) with hand hygiene practices among nurses, physicians, nursing assistants, and other HCWs was 39.1%, 27.1%, 31.1%, and 13.9%, respectively (p = 0.027). Easy access to handrub improved compliance (35.3% versus 50.6%, p = 0.035). Nurse status, working on morning shifts, use of the gel formulation, and availability of the alcohol-based handrub in the HCW's pocket were independently associated with higher compliance. Immediate accessibility was the strongest predictor. Based on self-assessment, observer assessment, and the measurement of epidermal water content, the gel performed significantly better than the liquid formulation. CONCLUSION: Facilitated access to an alcohol-based gel formulation leads to improved compliance with hand hygiene and better skin condition in HCWs.