Background:  prematurity is a global health problem with leading cause of infant death, mothers as the primary care giver need home care program of premature babies to ensure best practices and enhance their ability in attending to their infants' needs. Aim of the study: evaluate the impact of home care program on knowledge and practices of mothers of premature babies and their infants' physical growth. Research Design: A quasi experimental study with pretest-posttest nonequivalent groups design. Research hypothesis: The mothers with premature infants who received home care program have higher mean score of knowledge and practices, also, improvement of their infant's physical growth than those in the control group. Subjects and Method:  A purposive sample consisted of 184 mothers and their premature infants divided into two groups (study & control), 92 for each were selected from the premature outpatient follow up clinics attached to premature unit at Abu EL- Reish Pediatric hospitals and El Manial University hospital, Cairo University.  A structured interview questionnaire included demographic characteristics, Mother's knowledge and practices. In addition, growth measurement of the premature infants. Result: Mothers' knowledge and practice for caring premature infants were significantly higher than the total mean scores of those in the study group post and follow up program intervention (p=<0.000). Also, the premature infants in study group had good growth rate compared to the control group. Conclusion: the developed home care program led to significant improvement on mothers' knowledge and practices regarding caring of their premature infants, and consequently led to improve physical growth rates among their premature infants. Recommendation:  Interventions are needed to be given to mothers at home to improve their ability of caring their premature infants.