Background: Nurses' competency level in performing Basic Life Support is critical to improving the survival rate of cardiac arrest patients. As advanced technology and learning ways like simulation continue to evolve, it is vital for new as well as old nurse educators worldwide to have effectiveness in their teaching skills and abilities. Thus, Simulation is an evidence-based learning method and is widely used in the nursing educational field. Study aim: To determine the effectiveness of simulation-guided intervention on nurses' performance regarding basic life support. Study design: A quasi-experimental research design was used. Setting: The study was carried out in Critical Care and Emergency Nursing skill laboratories at the Nursing faculty, at Mansoura University. Study Subject: Convenience samples of 50 nurses were included from the previously selected settings that worked at intensive care and emergency units. Data collection tools: Tool I: structured interview questionnaire which included two parts related to personal data and nurses' knowledge regarding basic life support, and Tool I: nurses' practice regarding basic life support. Results: Showed that there were observed improvements in nurses' total knowledge and practice post implementation of simulation-guided by intervention regarding basic life support compared to pretest with statistically significant differences. Conclusions: Conclusion: Simulation- guided by intervention improved nurses' knowledge and performance in the field of basic life support.  According to the results, integrating conventional training with simulation-guided intervention can be effective in learning basic life support among nurses as an active learning strategies to develop nurses' performance in applying clinical skills. Recommendations: The latest guidelines of CPR should be available in written format in critical care units and emergency units. In-service education and training programs regarding CPR should be taught to all nurses. The use of educational resources such as simulator manikins allows participants to experience an emergent critical situation, take action, and review the consequences of choices. Repeat this research on a large sample size and in different settings for generalization.