Background: Nonsynostotic Plagiocephaly (NSP) is acquired cranial asymmetry that usually caused by external pressure on infant's skull. The aims, of this study were two folds: to evaluate the effect of Evidence-Based guidelines for prevention of nonsynostotic Plagiocephaly on nurses' and parent knowledge and to determine the effect of applying the Evidence-Based Guidelines on the occurrence rate of NSP. Design, A quasi experimental design was used in this study. Setting, the study was carried out in the following four health care centers in Menoufia Governorate in Egypt (the health center in Barakat Al-Sabaa, the health care unit in Barakat Al-Sabaa, and the health unit in the village of Al-Shaheed Fikry the health unit in the village of Al-Rawda). Sample, Convenience sample of 58 nurses and purposive sample of 295 mothers and their infants. Tools, three tools were used for data collection tool one: part one ,Nurses' Biosocial Characteristics Questionnaire, part two Nurses ‘knowledge assessment Questionnaire. Tool two, the Parents knowledge assessment Questionnaire. Tool three, Part 1: Biosocial characteristics for infants, and Part 2: Cranium assessment scale. Results, this study showed improvements in nurses' and parents' knowledge about the prevention of NSP in the study group post-intervention compared to the control group. Therefore, there are high statistical significance differences between pre and post- intervention in the study group at a 1% level of significance. The occurrence of nonsynostotic plagiocephaly among study group was (18.2%) at 4 months, while it decreased at 6 months it reaches (7.3%) after implementing evidence-based guidelines, instead of the control group which the occurrence of NSP reach 27.5% and 22% at 4 and 6 months respectively. Conclusions, implementation of evidence-based guidelines regarding prevention of nonsynostotic plagiocephaly significantly increases parents' and nurses' knowledge, also, it decreased the occurrence rate of nonsynostotic plagiocephaly among infant. Recommendation: Continuous training of evidence- based guidelines should be established in each maternal and child health care centers to enhance parents adherence to evidence base regarding preventive measure of nonsynostotic plagiocephaly.