Introduction: Exclusive breastfeeding (BF) is the cornerstone of child survival, nutrition, development and maternal health. Nursing intervention and health education regarding exclusive BF can improve knowledge, practice and attitude of mothers and contribute to prevention of exclusive breastfeeding discontinuation (BFD). Aim: To assess mothers' knowledge, practice and attitude regarding prevention of exclusive BFD. Design: A descriptive design was utilized. Setting: Obstetric Outpatient Clinic, Breast Feeding Room in NICU of Children's Hospital affiliated to Ain Shams University hospitals and MCH center in Abassia sector affiliated to Ministry of Health/ Cairo. Subject: A purposive sample of 100 mothers (24 primipara women at the third trimester and 76 lactating mothers to support maternity practices of exclusive BF). Tools: Predesigned questionnaire to assess: mothers and infants characteristics, knowledge regarding factors affecting exclusive BFD, Iowa Infant Feeding Attitude Scale and observational checklists to assess mothers' breastfeeding practice. Results: Less than one third of mothers of the studied mothers had good knowledge, only one fifth of the studied mothers had a positive attitude towards prevention of exclusive BF discontinuation and more than half of the studied mothers performed incompetent breast feeding practice. There was highly statistical significant difference between total knowledge of the studied mothers regarding exclusive BF, factors affecting exclusive BFD and total practice of breastfeeding (P-value =<0.001**). Conclusion: The majority of the studied mothers had poor knowledge, negative attitude towards prevention of exclusive BFD and incompetent BF practice. Recommendation: Developing pre and postnatal nursing intervention for protecting, promoting and supporting breastfeeding which aid in the prevention of exclusive BF discontinuation.