Arterial blood gases analysis considered a method for monitoring high-risk neonate's condition as it provides the basic information for determining the adequacy of alveolar ventilation, acid-base status and oxygenation. Nurses' attention should be given to the following factors; infection control or universal precautions as the neonates are at high risk of infection. Aim: The study aimed to evaluate the effect of a computer-based learning module on nurses' performance regarding safety arterial blood gases sampling for high risk neonates. Methods: A quasi-experimental research design conducted at Neonatal Intensive Care Units (NICUs) and Surgical Neonatal Intensive Care Unit "SNICU" of Benha Specialized Pediatric Hospital. A purposive sample of available nurses (62) and high-risk neonates (74). Researchers used three tools as Online nurses' self-administered questionnaire designed to assess nurses’ personal characteristics and nurses' knowledge regarding safe blood sampling for high-risk neonates. The second tool was nursing practice observation checklists. The third tool was High-risk Neonates' Medical Assessment Record. Results: Findings of the current study revealed a statistically significant difference pre and post computerized-based learning module implementation regarding safety arterial blood gases for high-risk neonates. The results also revealed a highly statistically significant difference in nursing knowledge and practices (p