BACKGROUND: Research suggests that patients could improve healthcare workers' compliance with hand hygiene recommendations by reminding them to cleanse their hands. OBJECTIVE: To assess patients' perceptions of a patient-participation program to improve healthcare workers' compliance with hand hygiene. DESIGN: Cross-sectional survey of patient knowledge and perceptions of healthcare-associated infections, hand hygiene, and patient participation, defined as the active involvement of patients in various aspects of their health care. SETTING: Large Swiss teaching hospital. RESULTS: Of 194 patients who participated, most responded that they would not feel comfortable asking a nurse (148 respondents [76%]) or a physician (150 [77%]) to perform hand hygiene, and 57 (29%) believed that this would help prevent healthcare-associated infections. In contrast, an explicit invitation from a healthcare worker to ask about hand hygiene doubled the intention to ask a nurse (from 34% to 83% of respondents; P <.001) and to ask a physician (from 30% to 78%; P <.001). In multivariate analysis, being nonreligious, having an expansive personality, being concerned about healthcare-associated infections, and believing that patient participation would prevent healthcare-associated infections were associated with the intention to ask a nurse or a physician to perform hand hygiene (P <.05). Being of Jewish, Eastern Orthodox, or Buddhist faith was associated also with increased intention to ask a nurse (P <.05), compared with being of Christian faith. CONCLUSIONS: This study identifies several sociodemographic characteristics associated with the intention to ask nurses and physicians about hand hygiene and underscores the importance of a direct invitation from healthcare workers to increase patient participation and foster patient empowerment. These findings could guide the development of future hand hygiene-promotion strategies.