Background: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR ion channel leading to abnormal secretions in multiple body systems and eventually respiratory failure. This study aimed to evaluate the compliance of educational protocol with parents' adherence to caring for their children with cystic fibrosis. A quasi-experimental design was utilized to conduct study. All available (40) parents accompanying their children with cystic fibrosis and attending the genetics outpatient and pediatric intensive care unit at El-Demerdash Hospital, affiliated with Ain Shams University Hospitals during study period (6 months). Five tools were used, namely Tool I: Personal and medical data sheet, Tool II: Self-reported practice questionnaire, Tool III: Care adherence scale, Tool IV: Barriers to treatment adherence scale and Tool V: Cystic Fibrosis Self Efficacy-Questionnaire. Study results shows that; less than three-quarters of the studied parents had poor levels of adherence to educational protocol, which improved to most of them had good levels of adherence at post and follow-up compliance educational protocol implementation. Study concluded that implementation of compliance educational protocol improved parents' adherence to caring for their children with cystic fibrosis. Study recommended similar studies on larger samples and regions to generalize the results.