Objective To explore the effect of nursing project management to prevent unplanned extubation (UEX) in emergency department observation unit (EDOU) patients. Methods UEXs in EDOU occurred between April 2020 and April 2021 were analyzed using root-cause analysis procedures, then 521 patients admitted to the EDOU from May 2021 to May 2022 were given nursing project management to prevent UEX. Nursing project management included refining the UEX prevention regulations and strategies, strengthening training and appraisal for nurses, optimizing patient education and feedback, increasing nursing workforce, and implementing continuous quality improvement measures. Results After the implementation of nursing project management, nurses′knowledge and practice of UEX prevention, as well as patients′ knowledge of UEX prevention were significantly enhanced, whereas the incidence of UEX was significantly reduced （all P＜0.05）. Conclusion The nursing project management for UEX prevention in EDOU improves nurses′ knowledge and practice, resulting in reducing UEX and ensuring patient safety.