background: As with any drug or medication, vaccines also require special attention because, though they are considered safe and beneficial to control diseases, they can trigger mild or even severe adverse events. Aim: assess nurse's knowledge and practice regarding adverse events of vaccines in expanded program on immunization in health care centers. Research design: A descriptive research design used in the current study. Setting: all available health care centers (14) & the only health office in Port Said city. Sample: All available nurses working in vaccination clinic, with total number of 64 nurses. Tools: data collected by two tools: tool one: Nurse's knowledge of vaccination and adverse event Questionnaire, tool two: observational checklists to assess nurse's practice about vaccination. Results: regarding the general knowledge of nurses of vaccines 96.9% of studied nurses had satisfactory knowledge, while 53.1% of studied nurses had satisfactory knowledge about contraindications of vaccines. 40.6% of nurses had unsatisfactory knowledge about adverse events of vaccines, moreover, 57.8% of the studied nurses had inadequate practice before and at the beginning of the vaccination session, while 93.8% of studied nurses had adequate practice during the vaccination session.Conclusion: most nurses had satisfactory score regarding overall knowledge of immunization, more than half of studied nurses had unsatisfactory knowledge regarding adverse event of vaccines. Moreover, more than half of studied nurses had inadequate practice. Recommendations: Establish training programs reinforce knowledge and practice of nurses related to adverse event of vaccines, continues training for nurses to keep them up to date in relation to immunization.