Background: Adherence to standards and policies and ongoing education are essential to maintain the quality of patient care and reduce potential negative transfusion outcomes. Aim: The study aimed to determine the effect of blood transfusion educational program on nurses' knowledge at intensive care units. Study design: A quasi-experimental study design was utilized in this study Setting: This study was carried out in the Intensive Care Units of six hospitals affiliated with the Egypt Health Care Authority in Port Said Gavernerate. Subjects: A purposive sampling technique was used to select 108 nurses at the intensive care units were included. Tools: Two tools were used for the collection of data, (I) Nurses' data and (II) Nurses' Knowledge Assessment Questionnaire. Results: The study findings revealed that knowledge among the majority of studied nurses was satisfactory and improved significantly post-educational program and during the follow-up period compared to the control group. There is a highly positive statistically significant relationship between nurses' knowledge and demographic data (educational level) at p ≤ 0.001. Conclusion: The current study concluded that the educational program implementation about blood transfusion had a positive effect on improving nurses' knowledge at intensive care units. Recommendation: Conduct similar studies in different settings and with different populations to enhance the generalizability of the findings. Also, scientific guidelines, posters, and written instructions about blood transfusion in intensive care units and to be included in the procedures.