Background: anticoagulants are high-risk drugs so it is very important to monitor the patients receiving anti-coagulant therapy. Aim: assess the nurses' performance regarding caring of patients on anticoagulant therapy in Port Said Hospitals. Subjects and Method: a descriptive research design was used A convenient sample of 130 nurses at three hospitals affiliated to Ministry of Health (Port-Said General Hospital, Port-Fouad General Hospital and El-Zohor Central Hospital) at Port-Said governerate were recruited. Tools: data were collected using three tools, nurses' knowledge assessment questionnaire, nurses' attitude scale and observational checklist for practice. Results: the result of study indicated that 66.9% of studied nurses had got unsatisfactory knowledge and 69.2% of them had got unsatisfactory practice while 60.8% of them had positive attitude regarding anticoagulant therapy. Conclusion: the study concluded that more than two thirds of the studied nurses had unsatisfactory knowledge, practice and less two thirds of them had positive attitude regarding caring of patients on anticoagulant therapy and there were a highly statistically significant positive correlation between total nurses' knowledge, practice scores and their total attitude scores .In addition, there is no statistically significant relations between total score of nurses' knowledge, practice, and attitude and all items of personal characteristics and work related data. Recommendations: There are obvious needs for conducting educational and training programs to improve nurses' knowledge and practice regarding the care of patients undergoing anticoagulant therapy.