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This study assesses the impact of religiosity on delirium severity and patient outcomes among Shi'a Muslim intensive care unit (ICU) patients. We conducted a prospective observational cohort study in 21 ICUs from 6 Iranian academic medical centers. Delirium was assessed using the Confusion Assessment Method for the ICU (CAM-ICU) tool. Eligible patients were intubated, receiving mechanical ventilation (MV) for ≥ 48 h. Illness severity was assessed using Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. A total of 4200 patients were enrolled. Patient religiosity was categorized as more (40.6%), moderate (42.3%), or less (17.1%) based on responses to patient and surrogate questionnaires. The findings suggest that lower pre-illness religiosity may be associated with greater delirium severity, MV duration, and ICU and hospital LOS. The lower mortality in the less religiosity group may be related in part to a greater proportion of female patients, but it remains unclear whether and to what extent greater religiosity impacted treatment decisions by patients and families. Further investigation is needed to validate and clarify the mechanism of the mortality findings. [ABSTRACT FROM AUTHOR]