Background: Pathological jaundice is the most encountered medical problem in the first one week of life. Bilisphere phototherapy is a new modality in management of pathological jaundice. Nurses play an important role in achieving optimal outcomes for neonates under bilisphere. Aim of the study: This study aimed to evaluate the effect of education program regarding bilisphere phototherapy on nurses' performance and outcomes of neonates with pathological jaundice. Research design: A quasi-experimental research approach was used. Setting: This study was carried out at Benha Specialized Pediatric Hospital, Neonatal Intensive Care Units. Study subjects: A convenient sample of all nurses who work in the aforementioned setting and a purposive sample of newborns selected for the study. Data collecting tools: Three tools were employed: Tool I: A structured interviewing questionnaire sheet consisted of 4 sections, Tool II: Observational checklist for caring neonates under bilisphere and consisted of 3 sections, Tool III: Neonatal outcomes evaluation sheet: It consisted of 2 sections. Results: The majority of the studied nurses had satisfactory knowledge and competent practice after-education program implementation. Conclusion: The outcomes for neonates (study group) and the performance of nurses were positively correlated after- program implementation. Recommendations: Periodical in-service education programs regarding pathological jaundice should be designed and implemented to improve nurses' knowledge based on nurses' actual needs.