Hand hygiene is the simplest and most effective measure for preventing healthcare-associated infections. Despite the simplicity of this procedure and advances made in infection control, hospital health care workers' compliance to hand hygiene recommendations is generally low. Nurses have the most frequent patient care interactions, and thus more opportunities to practice hand hygiene. As such, it is important to identify and understand determinants of nurses' reported compliance. Formative research was undertaken to assess the potential impact of several unexamined factors that could influence HH among nurses: professional role and status, social affiliation, social norms, and physical modifications to the work environment (as well as institutional factors like safety climate). A survey questionnaire was developed primarily to inform the creation of a behaviour change intervention. The survey looked at how these factors influence HH among nurses and sought to identify barriers and levers to reported hand hygiene. It was administered to a survey panel of acute care nurses, working in US hospitals, with a year or more of experience. Multivariate regression modelling suggested that reported hand hygiene compliance was most likely to be a function of a hospital management's communication openness, perceived performance by peers, increased interactions with patients and other staff members, and the reduction in stress, busyness, and cognitive load associated with role performance. A powerful, effective intervention on HH among nurses therefore could be directed at improving communication openness, consider the impact of perceived performance by peers, increase interactions with patients and staff, and determine how to reduce the stress and cognitive load associated with role performance.