Background Extracorporeal membrane oxygenation (ECMO) has become an important form of organ support for patients with severe circulatory or respiratory failure, as a bridge to recovery or more definitive treatment options. Therefore, this demands a more efficient performance by the nursing staff, to achieve optimum results. Aim: The study aims to assess the effect of educational guidelines on nurses' performance regarding caring for patients on extracorporeal membrane oxygenation and patient outcomes. Design: A quasi-experimental (one group pretest/posttest) design was utilized in this study. Sample: A convenience sample of all available nurses (50 nurses) and a convenience sample of 40 patients to assess patient outcomes. Setting: The study was conducted at a critical care unit affiliated to Sohag University Hospitals, Egypt. Tools: From the previous method setting, three tools were used to perform the study, 1- a Nurse Knowledge Assessment Questionnaire and 2- Nurse' Observational Checklist were utilized 3- patients outcomes questionnaire. Results: the result showed that that 54% of the studied nurses were between the ages of > 26- <35 years with a mean age of 31.82±7.6. About gender, 62% were males, 72% were single, and 86% had a bachelor's degree in nursing.  And 96% of the studied nurses had a satisfactory level of knowledge and 98% of nurses had an adequate level of practice regarding ECMO post-implementing of intervention guidelines. Regarding to patient outcomes 37.5% of the studied patients have Acute respiratory failure as a medical diagnosis. About Types of ECMO Modalities, 77% were put on VV mode, and 75% were put on central ECMO cannulation also15.76±4.33 was the mean number of days on ICU and7.43±3.16 was the mean number of days on ECMO and 10.98±5.74 was the mean number of days on mechanical ventilator. Regarding ECHMO complications 15% of them had renal and pulmonary complications. Conclusion: Based on the results of the present study, it can be concluded that the implementation of educational guidelines had a statistically significant positive effect on total knowledge and practice satisfactory levels in the pre-, and immediate post-tests. There was a highly statistically significant difference regarding nurses' total level of knowledge and practice regarding ECMO complications rate, which supported the research hypothesis. Recommendations: Conduct training programs for the nurses caring for patients on ECMO machines.  Providing nurses caring for patients on the ECMO machine with a designed instructional Arabic booklet and pamphlet regarding how to deal with the ECHMO machine.