Purpose: This study aimed to develop an evidence-based extracorporeal membrane oxygenation (ECMO) nursing protocol for critically ill patients receiving ECMO treatment by using an adaptation process, and to verify the effects of the protocol. Methods: The protocol was developed according to the adaptation guidelines. A non-randomized controlled trial was conducted to test the protocol’s effects. Data were collected between April 2019 and March 2021. The differences in physiological indicators and complication rates between the two groups were investigated using a chart review to evaluate patient outcomes. The nurses’ outcome variables were evaluated using a questionnaire. Results: First, after reviewing 11 guidelines by appraisal of the guidelines for research and evaluation collaboration II, 5 guidelines with a standardization grade of over 50 points were selected. An ECMO nursing protocol was developed based on these guidelines. Second, there were no statistically significant differences in physiological indicators between the two groups of patients. However, the experimental group showed a statistically significant decrease in the infection rate (p = .026) and pressure injury rates (p = .041). The levels of satisfaction with ECMO nursing care, and empowerment and performance of the nurses who used the ECMO nursing protocol were higher than
those of nurses who did not (p < .001). Conclusion: This protocol may help prevent infections and pressure injuries in patients, and improve nurses’ satisfaction and empowerment. The nursing protocol developed for critically ill patients receiving ECMO treatment can be utilized in evidence-based nursing practice.