Background: Creative management and mindfulness are becoming critical to the success of future head nurses as they will heighten cohesion, productivity, and work thriving among staff nurses, as well as encourage nursing professional autonomy. Aim: The study aimed to assess creative management and mindfulness and its relations to nurses` work thriving and professional nursing autonomy. Design: Descriptive correlational design was utilized. Setting: The study was conducted in all inpatient units (55) of Benha University Hospital. Subjects: Consisted of all available head nurses (55) and a simple random sample of 327 staff nurses out from 1800 working in the above-mentioned setting. Tools of data collection: Four tools were used; Creative Management Questionnaire, Five Facet Mindfulness Questionnaire, Thriving at Work Scale, and Professional Nursing Autonomy Scale. Results: More than two-thirds (70.9%, 69.1%) of head nurses had moderate levels of perception regarding creative management, and tendency toward mindfulness respectively. In addition, about two-thirds (64.8%) of staff nurses had moderate levels of work thriving, and more than half (59.6%) of them had moderate perception levels regarding professional nursing autonomy. Conclusion: There was a highly statistically significant positive correlation between the total head nurses' perception of creative management and tendency toward mindfulness and total levels of staff nurses' work thriving and perception of professional nursing autonomy. Recommendations: Setting specific mechanisms for the selection of creative head nurses and for maintaining creative management. In addition, developing and implementing a training program to enhance the head nurses' mindfulness which in turn has a positive effect on nurses' thriving at work.