Background: Premature infants' admission to a Neonatal Intensive Care Unit (NICU) may adversely impact on mother's psychological status, typically experience high stress levels, anxiety, and depressive symptoms and low of confidence. Aim of the study: This study aimed to evaluate the effect of an empowerment program on Psychological Distress and Parenting Confidence in Mothers of Premature Infants Admitted to Neonatal Intensive Care Unit. Research Design: A quasi - experimental design (one group pre test- post test design) was utilized to achieve the aim of this study. Setting: The study was conducted at Neonatal Intensive Care Unit at Benha University Hospital which was linked to Ministry of Higher Education, Qalyubia Governorate. Sample: A convenience sampling consisted of 60 mothers having premature infants admitted to Neonatal Intensive Care Unit at Benha University Hospital. Tools: For data collection, the following tools were used: I) A structured interviewing questionnaire included socio-demographic data and clinical data of mothers and infants, II) Parental stress scale (PSS), III) The Beck Anxiety Inventory (BAI), IV) The Edinburgh postnatal depression scale (EPDS) and V) Karitane Parenting Confidence Scale (KPCS). Results: More than half of the studied subjects reported severe psychological distress, and more than two-thirds had low parenting confidence prior to the implementation of the empowerment program, while nearly two thirds of them had high confidence after implementation of the program. Also, there was a highly statistically significant negative association between their overall level of confidence and their overall levels of stress, anxiety, and depression post program implementation. Conclusion: The maternal empowerment program had a positive effect on reducing psychological distress and improving parenting confidence among mothers of preterm babies admitted to the Neonatal Intensive Care Unit. Recommendations: It is recommended to conduct more research with larger sample size and longer follow-up times at various intervals.