Delirium is one of the most commonly encountered problems among patients in the Intensive Care Units (ICUs) resulting in increased duration of mechanical ventilation and length of stay. Nurses' knowledge and practice had an important impact in improving the quality of healthcare and preventing delirium in patients. The study aimed: To evaluate the impact of psycho-educational program on nurses' knowledge and practices regarding care of patients with delirium. Subjects & Method: A quasi-experimental research design was utilized in this study, conducted at intensive care units at AL-Thawra Hospital – Yemen. The study incorporated a convenience sample of (60) nurses working in the ICUs. Data collection tools included demographic and work-related characteristics data, nurses' knowledge questionnaire of delirium and observational checklist for assessment of nurses' practices caring for delirium patients. Results: There is a marked improvement in ICU nurses mean scores of their knowledge and practices regarding caring patients with delirium immediately after program implementation and follow up. Conclusion: The psycho-educational program has positive effect on nurses knowledge and practices regarding caring for patients with delirium after implementing the educational program. Recommendations: Periodic monitoring of nurses' knowledge and practices to evaluate the level of nurses' practice about delirium and construct program according to their needs.