Background: Entrepreneurial orientation and knowledge management Knowledge Management process are considered the most common approaches for organizational development and strength in the present competitive environment. Aim: The study aimed to assess the association between the entrepreneurial orientation and Knowledge Management process among first line mangers. Setting: The study carried out in inpatients units (57) of Benha University Hospital. Research design: A descriptive correlational design using self-administered questionnaire was used. Sample: All first line nurse managers (80) completed the Perceived Entrepreneurial orientation scale and knowledge management instrument. Results: More than two thirds of first line mangers had low level of entrepreneurial orientation also the majority of them had low level of knowledge management. The highest mean score of first line mangers entrepreneurial orientation was relevant to autonomy, while the lowest mean score was linked to aggressive competitiveness. Regarding to knowledge management process, the highest mean score were related to knowledge sharing, while the lowest mean score was related to knowledge storing. Conclusion: The majority of first line mangers had low level in both entrepreneurial orientation and knowledge management. There was a significant association between entrepreneurial orientation and knowledge management process. Recommendations: Autonomy and competitive disaggressiveness should be supported and promoted to improve first line mangers level of entrepreneurial orientation; hospital managers should be enhance sharing and developing knowledge to improve practice of the work; effective organize the knowledge by using modern informational technologies or traditional means to share and storing the organized knowledge at all managerial levels to overcome challenges.