Background: Entrepreneurship has the potential to increase the visibility of the nursing profession and create new spaces for nurses. Being creative and entrepreneurial in the nursing profession, improving health services and patient safety, is seen as a prerequisite for achieving excellence in the health sector. Aim: the study aimed to assess effect of entrepreneurship educational program on head nurses' entrepreneurial intentions and attitude. Design: A quasi-experimental research design was utilized in this study. Setting: The study was conducted at El Hussein University Hospital, Cairo, Egypt. Subjects: A simple random sample (80) from head nurses was included. Data collection tools: Three tools were used for data collection (1) Entrepreneurship knowledge Questionnaire, which included demographic data, (2) Entrepreneurial Intention Questionnaire, and (3) Entrepreneurship Attitude Questionnaire. Results: There was a highly statistically significant difference in total knowledge, intention and attitude pre, post and follow up applying entrepreneurial educational program. There were significant statistical positive correlations between head nurses’ total entrepreneurial knowledge and attitude and entrepreneurial attitude and intention of head nurses. Conclusion: The educational program for head nurses was effective and improved their level of entrepreneurial knowledge, intention and attitude. Recommendation: Creating a supportive environment that fosters nurses' independence and encourages them to take risks that foster their creativity and entrepreneurship.