Hand hygiene (HH) is widely regarded as the single most effective method of preventing healthcare-associated infections yet achieving and maintaining compliance among healthcare workers remains a significant challenge. This study aims to identify behavioral determinants of HH compliance using the Attitude-Social Influence-Self-Efficacy (ASE) model among Intensive Care Unit (ICU) nurses in Saudi Arabia. This is a descriptive cross-sectional study using a self-reported questionnaire among ICU nursing staff in 6 Ha’il, Saudi Arabia hospitals. The study employed convenience sampling, using the Behavioral Determinants of Hand Hygiene Compliance in ICU questionnaire with 128 respondents. Frequency, percentage, mean, standard deviation, ANOVA, Pearson-r, and Multiple Regression analysis were used. Total compliance to HH for six hospitals was 86.83%. Self-efficacy was high (mean=3.59, SD=.54). The average score of participants’ knowledge of HH was 57% (SD=2.30). Only social pressure was identified as a predictor of noncompliance to HH (β=-1.97; P=.001). The current data highlight the importance of self-efficacy, social influence, positive attitude, and good knowledge regarding HH. However, only social pressure was a predictor of compliance with HH guidelines. When developing interventions to improve HH in ICUs, strategies should include these determinants tailored to the individual, cultural, and institutional factors.