Background: Patients' safety in emergency operating room is an essential part of nursing practice so that, nurses must be equipped with appropriate knowledge and skills to meet the needs of such group of patients safely and competently. Aim: This study aims to evaluate the effect of designed nursing guidelines regarding patients' safety in emergency operating room on nurses' performance.  Design: One-group quasi-experimental (pre-post) research design was utilized. Setting: the study was conducted at emergency operating unit which affiliated to Ain Shams University Hospital at Cairo - Egypt. Sample: A convenience sample of 40 nurses from the previously mentioned setting were recruited in the current study. Tools: Four tools were be used to collected data to achieve the aim of the present study as following I-Nurses' structured self-administered questionnaire, II-Nurses' practice observational checklist, III- Nurses' attitude scale regrading patients' safety and IV- Nurses' opinion sheet regarding the effectiveness of nursing guidelines. Results: There was statistically significant improvement in the studied nurses' knowledge and practices regarding patients' safety in emergency operating room post the designed nursing guidelines implementation as 92.50% & 95 % respectively. In addition to, the total satisfactory level of the studied nurses' attitude regrading patients' safety was 90 % post the designed nursing guidelines implementation. Conclusion:  the results of current study concluded that, majority of the studied nurses had a significant improvement in their performance (knowledge, practices & attitude) regarding patients' safety in emergency operating room post nursing guidelines implementation compared to pre. Recommendations: Emergency operating room should be supplied by evidence -based protocols regrading safe surgery in order to reduce the risk of unnecessary harm associated with emergency surgical procedures.