Plasmapheresis is a medical procedure that involves the extraction, substitution, or exchange of blood plasma externally from the body. Nurses hold a crucial role within the multidisciplinary team in executing and supervising the plasmapheresis treatment. The aim of this study was to assess the impact of designated evidence-based guidelines on nursing performance among patients with autoimmune disease undergoing plasmapheresis. Design: A quasi-experimental research design utilizing a pretest and a posttest will be employed to fulfill the aim of this study. Sitting: This study was performed at the therapeutic plasma exchange room in the Hemodialysis unit in Ain Shams University Hospital affiliated to Ain Shams University. Tools: A structured interview questionnaire for nurses comprised two sections: Section 1: Demographic Attributes of Nurses, Section 2: Nurses' knowledge of the Plasmapheresis Procedure. Result: 33.3% of the studied nurses exhibited good knowledge before the intervention, which increased to 76.7% post-intervention, indicating highly statistically significant differences, also this study showed improvement in nurses’ level of practice regarding plasmapheresis 53.3 % competent level of practice pre intervention become 93.3 % competent level of practice post intervention. Conclusion: The results indicated that the implementation of specific evidence-based guidelines markedly improved nurses' knowledge and practice. This study emphasizes the significance of incorporating evidence-based guidelines into clinical practice and ensuring continuous education and training for nurses. Recommendations: Evidence-based guidelines should be implemented as a standard protocol in all units where plasmapheresis is performed and the Nursing curriculum should incorporate the best evidence based protocols for procedures such as plasmapheresis, ensuring that graduated nurses are well-prepared.