Background/aims Hand hygiene is recognized globally as a leading measure to reduce healthcare-associated infection. However, compliance with hand hygiene is unacceptably low. Physicians − in particular − have repeatedly been observed to be poor compliers. Promotion of this important practice is a complex issue. It is important to study the behavioral determinants in relation to hand hygiene practices to develop effective improvement strategies. The aims of our study are to assess the knowledge of the physician and their attitudes and practices of hand hygiene, to identify the behavioral determinants of noncompliance, and to recommend interventions that could increase the practice. Participants and methods An anonymous questionnaire was administered that included four sections: participants’ demographic data, self-reported compliance on the basis of the Centers for Disease Control and Prevention Guidelines, attitudes in relation to the studied behavior adapted from a validated published questionnaire, and the knowledge assessment section chosen from the WHO questionnaire. The questionnaire was distributed by infection control practitioners at King Saud Medical City − a tertiary care hospital in Riyadh, Saudi Arabia − and self-completed by 127 physicians of different specialties during March–May 2015. Results The response rate was 75%. The mean self-reported compliance rate was 89.4%. A multiple linear regression analysis was carried out on the studied variables that identified three main predictors most likely to be correlated with hand hygiene behavior noncompliance: self-efficacy (β=0.252; P=0.004), time-related attitude (β=0.16), and usefulness-related attitude (β=0.148). Conclusion Understanding the determinants of a fundamental behavior such as hand hygiene in healthcare settings is among the essential steps to plan more effectual intervention strategies for compliance improvement. Contributions from behavioral and social sciences are crucial when designing studies to investigate and improve behavior acquiescence. The healthcare system is complex and more studies are needed to elaborate specific behavioral determinants in relation to the practice of hand hygiene in other variable work situations and among different healthcare workers categories and employee belong to different culture group.