Background: An external fixator is a device used to stabilize a broken bone and facilitate deformity correction. Pin site infection is still a serious complication of external fixation. These patients also suffer from pain, discomfort, and anxiety due to any adjustment techniques and movement of pins through skin. Purpose: To assess effect of orthopedic nursing care protocol on nurses' knowledge, performance, and patients' outcomes among patients with external fixators. Setting: The study was conducted in Orthopedic Surgery Department, University hospital, Menoufia, Egypt. Sampling: Convenience sample of nurses working in orthopedic surgery department (32 nurses) and a purposive sample of 76 adult patients who were undergoing external fixation. They were divided into two equal groups (study and control). Instruments: Six instruments were used: Subjects' and Nurses' Interviewing Questionnaire; Nurses' Knowledge Assessment Questionnaire; Nurses' Observational Checklists; Checketts Otterburns Grading System for pin site infection; The Numeric Pain Rating Scale; and Beck Anxiety Inventory. Results: The study finding displayed a highly significant improvement in the nurses' knowledge and performance scores in the posttest compared to pretest with p-values <0.001. Concerning to the patients outcomes, the study results revealed statistically significant difference between the study and control groups regarding pain, anxiety levels and pin site infection in favor of study group when comparing the two groups, with p-values <0.05. Conclusion: The study findings concluded that the nursing protocol has positive effects in improving nurses' knowledge and performance related to care of orthopedic patient with external fixators and led to a lower levels of pain and anxiety and decrease in pin site infections among the subjects of the study group when compared to the control group. Recommendations: Orthopedic nurses should attend regular in-service training courses and workshops on external fixators, focusing on their weaknesses. This will improve their knowledge and practice, ultimately leading to better patient outcomes.