Context: Plasmapheresis considered as safe, fast and powerful therapeutic approach for chronic disease management through removing destructive antibodies and toxins from patient's blood. Aim: to evaluate how educational guidelines implementation can affect nurses' knowledge and practice regarding plasmapheresis process. Methods: The study used a quasi-experimental design, specifically employing a pre/post-test methodology on a convenience sample of (60) nurses who assigned to care for patients who underwent to plasmapheresis. This study was conducted in the hemodialysis unit at Benda University Hospital. The study utilized the following tools: I) Self-administered questionnaire consisting of nurses' personal data and knowledge assessment sheet.  II) Observational checklist to evaluate nurses' skills before, during, after plasmapheresis. Results: 16.7% of studied nurses had satisfactory level of total knowledge about plasmapheresis process pre guidelines implementation to be significantly improved during immediate and post three months of guidelines implementation among 76.7% & 66.7% respectively. While 20.0% of studied nurses had satisfactory level of total practice about plasmapheresis process pre guidelines implementation to be significantly improved during immediate and post three months of guidelines implementation among 70.0% & 63.3%, respectively. There was a highly significant difference in total nurses' knowledge and practice score within study periods observed as p <0.001. Conclusion: Educational guidelines implementation effectively improved nurses' knowledge and practice toward plasmapheresis process. Recommendation: Conduction ongoing educational programs for nurses to update their performance is necessary.