HAIs have become a key burden at the global level, and there is a persistent disconnect between the official formulation of the policies on infection control and prevention (IPC) and their successful application to clinical practice, which is especially applicable to the situation in the complicated healthcare environment of Saudi Arabia. The current study aimed to examine the mechanistic relationship between IPC policy quality and HAI outcomes in a tertiary care unit. The mixed-method sequential explanatory design was implemented over 6 months in three clinical units. Information involved policy audits, direct observation of the compliance of healthcare workers (HCW), validated surveys, prospective HAI surveillance, and in-depth interviews. The hierarchical regression model showed that IPC policy score ( -0.348, p =.002) and HCW compliance ( -0.590, p <.001) had significant negative predictive values of HAI incidence and had a 94.2 percent variance. Perceived barriers were found to be a central process in mediation analysis, which explained 52.1 percent of the impact of policy on compliance. The results show that frontline adherence is a critical mediator of the effect of IPC, and frontline adherence is also greatly affected by barriers that are context-specific. This explains why IPC strategies need to go beyond the development of policies and move to contextual and behavioral determinants to enhance patient safety.