Background: Infection control in hospitals remains a challenge to healthcare policymakers and world healthcare leaders. This study was aimed to explore the factors associated with self–reported awareness, approach, and application of infection control practices and to describe the barriers and enablers to such practice among registered nurses in all intensive care units (ICUs) at King Salman Armed Forces Hospital in Tabuk, Kingdom of Saudi Arabia. Methods: A cross–sectional, descriptive and comparative study was conducted from January 2016 to June 2016. One hundred twenty–four registered nurses voluntarily participated in the study. Data was collected using a self–reported questionnaire. The data was analyzed using IBM Statistical Package for Social Sciences (SPSS) version 25 for Windows. Descriptive statistics and one–way ANOVA were used to analyze the data. Results: The registered nurses demonstrated high level of awareness, approach, and application of implementing infection control standard and guidelines. No statistically significant differences were found between mean awareness scores in age, gender, and education. Statistically significant differences were found between mean application scores in age and current working unit (p–values 0.05, 0.009 respectively). Conclusion: The awareness and application of implementing infection control standards and guidelines among the registered nurses were good. However, there is still a wide scope of improvement with regular educational training programs.