Reducing the incidence of healthcare-associated infection represents a major challenge. This systematic review of the evidence base considers the clinical effectiveness of incorporating an alcohol-based hand hygiene product into procedures aimed at improving compliance with hand hygiene guidelines, and thereby reducing the incidence of healthcare-associated infections. Multi-component interventions that included alcohol-based products were as effective as those that did not, both in achieving sustained hand hygiene compliance and in reducing infection rates. However, a number of difficulties were encountered in assessing hand hygiene studies: the problem of attributing efficacy to an alcohol-based product when used in a multi-component intervention; the variability inherent in the design of such studies; and how to use data from uncontrolled, unblinded studies in the assessment.