Extracorporeal Membrane Oxygenation (ECMO) is an advanced life support machine being used with patients with respiratory failure and/ or cardiac failure. ECMO is a complicated medical care that requires diligent nursing care. Critical care nurses with the knowledge and practice can potentially reduce the risks of morbidity and mortality in these patients. Aim: to assess the nurses’ knowledge and practice regarding care of patients connected with ECMO. Design: A descriptive exploratory design was utilized in this study. Setting: The study was conducted at critical care department at Cairo University Hospitals. (Critical care unit in Qasr Al-Aini Hospital). Sample: A convenience sample of all available nurses (60 nurses) from both genders. Tools: Data were collected by using two tools; the first tool is self- administered interview questionnaire, and the second tool is nurses’ observational checklist regarding care of patients connected with ECMO. Results: the current study showed that 88.3% of studied nurses had a satisfactory level of knowledge regarding care of patients connected with ECMO, and 78.3% of studied nurses had a competent level of practice regarding care of patient connected with ECMO, there wasn’t a statistically significant relation between total level of knowledge regarding care of patients connected with ECMO and demographic characteristics, while there was a highly statistically significant relation between total level of practice regarding to care of patients connected with ECMO and demographic characteristics. Conclusion: there were highly statistically significant positive correlations between the studied nurses’ total level of knowledge and their total level of practice regarding care of patients connected with ECMO. Recommendations: Continuing assessment of nurses’ knowledge and practice, continuous training courses should be conducted for nurses to improve their knowledge and practice and to increase their performance regarding care of patients with ECMO