Surgical safety has been a major challenge of the nursing profession. Much progress has been made in identifying what causes errors, and understanding the relationship between safety and patients' outcomes. Aim: To evaluate the effect of nurses' implementation of surgical safety guidelines on their performance and post-operative complications. Design: A quasi-experimental research design was used. Setting: The study was conducted at the operating room and general surgery department at the university hospitals in Cairo. Sample: A convenient sample of 72 nurse and 100 patients at the general surgery department. Tools: Four tools were used: I: self-administered questionnaire it included: demographic characteristics of the nurses and nurses' knowledge assessment questionnaire, II: Nurses' safety practices observational checklist. III: Safety attitude questionnaire, IV: Post-operative Complications Questionnaire: It included demographic characteristics of the patients and post-operative complications. Results: There were high statistically significant differences between nurses' mean scores of knowledge post implementation of surgical safety guidelines. All of anasthesia nurses performed surgical safety practices, there were highly statistically significant differences between nurses' attitudes regarding reporting any safety concerns and working with physicians as a team. As well; there was highly statistically significant reduction of some post-operative complications post implementation of surgical safety guidelines. Conclusion: Nurses' implementation of surgical safety guidelines had a positive effect on their performance and on reduction of post-operative complications. Recommendations: Surgical safety guidelines should be implemented as part of daily surgical routine and encourages its use to all surgical operations.