Background: Nursing informatic is a crucial field in healthcare that require specialized training and follow up to adequately develop the knowledge and skills required by nurses to utilize health information technology. Aim: To examine the effect of nursing informatics training program on nurse interns’ knowledge and skills. Design: A quasi-experimental design was utilized in this study. Setting: The study was conducted at Faculty of Nursing at Cairo University. Subjects: a convenient sample of nurse interns (n=30) who trained in critical care area. Tools: Two tools were utilized 1- nursing informatics knowledge questionnaire (50 items) 2- electronic medical record auditing checklist (25 items). Results: The study revealed that there were a significant statistical differences in total knowledge test scores and knowledge dimensions during diffrent periods of assessment. The total mean score across all dimensions increased significantly from x̄= 25.70 pre-program to x̄=37.47 post-program and x̄=33.97 at follow-up. Additionally, there were a statistical significant differences in total mean scores of nurse interns nursing informatics skills, with the overall total mean score increased from (x̄=17.23) post-program to (x̄=19.86) at follow-up. Conclusion: The current study found a significant improvement in nurse interns nursing informatics knowledge test scores, and informatics skills immediately and three months after program implementation. Recommendations: Academic institutions should incorporate comprehensive nursing informatics curricula into their nursing education programs, Healthcare administrators should provide ongoing nursing informatics education and training to nursing staff at regular intervals.