Background: There is widespread interest in measuring nursing perception about issues relevant to patient safety to ensure both the individual health care providers and health care system to contribute to safe delivery of care.  The present study aims to assess staff nurses' perception toward working conditions affecting patient's safety at Sherbeen General Hospital and Mansoura New General Hospital. A descriptive comparative study was utilized with a sample of 204 staff nurses in Sherbeen General Hospital and 250 staff nurses in Mansoura New General Hospital. Data were collected by using the hospital survey of patient safety culture questionnaire.  Results revealed that, the highest percent of staff nurses' perception at Sherbeen General Hospital was shown in personal and social factors but at Mansoura New General Hospital was in hospital environmental factors. In conclusion, the staff nurses' at Mansoura New General Hospital were highly perception withhealth care working condition that affect patient safety than Sherbeen General Hospital, there was statistically significance difference between the staff nurses' perception in both hospitals regarding the personal and social factors. The study recommended that there should be a blame-free environment for identifying threats to patient safety, sharing information and learning from events. Nurses should be focused in area of errors as shift changes, patient transition and handover