Immunoglobulin is a pooled antibody, and a biological agent used to manage various immunodeficiency states. Immunoglobulin therapy requires an advanced standardized clinical practiced nurse to ensure safety and good clinical outcomes. Aim is to evaluate the effect of the implementation of Educational Guidelines for Nurses regarding the Safety Practice of Immunoglobulin Administration on their Knowledge and Performance. Research Design A quasi-experimental study was implemented. Setting: the study conducted at Internal Medicine Hospital of Tanta University. The involved departments were Internal Medicine ICU, Rheumatology, Hematology, Endocrine. Subject: purposive sample of 47 nurses recruited in the previous departments. Tools : three tools were used in this study Tool I:Self-assessment of Nurses' Knowledge Questionnaire. Tool II: An Observation Checklist for Standard of Practice of administering Immunoglobulin. Tool III" An Observation Checklists of Nurses' adherence to safe Practice . Results: There were a significant improvement related to total nurse's knowledge mean score about immunoglobulin therapy after educational guidelines . Also a high significant in mean score of observed safety practice adhered from the nurses. In addition to a high and positive correlations between total level of knowledge and practice about safe administering IG therapy. Conclusion: Implementation of educational guidelines has a positive impact not only in improving nurses' knowledge but Safety Practice of Immunoglobulin administration. Recommendation: It is recommended that nurses should attend continuously in-service training programs for improving their knowledge and enhancing their safety practice in relation to immunoglobulin IV infusions. Also other researches needed to be on replication to generalize the results.