Background: Diabetic ketoacidosis is an acute, major, life-threatening complications of diabetes. Nurses' knowledge and practice play important role in provision of supportive care to decrease morbidity and mortality secondary to diabetic ketoacidosis. Patient safety is influenced by many factors, identification of these factors can prevent harm and protect patients from any associated complications. Aim: was to assess the factors affecting the patients safety with diabetic ketoacidosis in intensive care unit. Design: A descriptive exploratory design. Setting: The study conducted in intensive care unit at Fayoum University Medicine Hospitals. Sample: A convenient sample of all available nurses (no=30) and patients with diabetic ketoacidosis admitted to intensive care unit (no=70). Tools of data collection: self-administered questionnaire, nurses' practice observational checklist, patients interviewing questionnaire and patients complications assessment sheet. Results and conclusion: Regarding nurses related factors more than half of the nurses had satisfactory level of knowledge and practice regarding safety nursing management of patients with diabetic ketoacidosis (56.7% and 60%) respectively. Also, (63.3% & 70%) respectively of them had satisfactory level regarding factors affecting patients safety. Regarding general nursing safety measures related factors, (73.3%) of the nurses had satisfactory level regarding infection control measures in intensive care unit and (50%) of them had unsatisfactory level regarding medications administration measures. In relation to organizational related factors (73.3%) of the nurses had satisfactory level regarding sufficient staffing and (33.3%) of them had unsatisfactory level regarding hospital facilities and equipment. Regarding patients related factors (61.4%) of them had unsatisfactory level of knowledge regarding diabetic ketoacidosis safety management and (7.1%) of them had diabetic ketoacidosis associated complications. Recommendations: Importance of in-service training courses to enhance the nurses knowledge and practice regarding patients safety with diabetic ketoacidosis in intensive care unit to decrease morbidity and mortality rate.