Background: Cerebral angiography is a standard invasive and diagnostic procedure with great sensitivity. It is used for the diagnosis of a wide range of cerebral problems. Aim: Was to evaluate the effect of designed protocol on critical care nurses' performance regarding cerebral angiography and patients' outcomes. Design: A quasi experimental design was used. Setting: study conducted in Neurological Intensive Care Unit at Zagazig University Hospitals. Sample: A Convenient sample of 30 nurses and all available patients (30) undergoing cerebral angiography. Tools: Five tools were utilized; Interviewing questionnaire for nurses; observational checklists for nurses, interviewing questionnaire for patient, vascular complications assessment questionnaire, and Critical-Care Pain Observation Scale. Results: Mean scores of nurses' knowledge and practice increased significantly after designed protocol. Also, 60% of studied patients had subarachnoid hemorrhage and 53.3% were diabetic, 86.7% were hypertensive and 66.7% had interventional cerebral angiography, 93.3% of studied patients had headache and 53.3% had fainting. Also, there was a statistical significant decrease in hematoma formation and access site symptoms after designed protocol, in addition to significant decrease in pain. Conclusion: There was a significant improvement of critical care nurses' knowledge and practice after the designed protocol, which reflected then on improvement of patients' outcomes through reduction of postoperative complications for patients undergoing cerebral angiography and pain improvement. Recommendations: Continuous training program should be applied for critical care nurses regarding care of patients undergoing cerebral angiography for updating their knowledge and practice.