Purpose: This research was conducted to evaluate the effects of asystemic follow-up care program on health promotion and risk reduction in 64 high-risk infants(HRI) including premature infants and their mothers. Method: The intervention consisted of systemic NICU education, tele-counseling and 3 home visits in 6 months. The subjects were divided into either the intervention group or the control group receiving the conventional NICU education without the tele-counseling and home visiting. Infant health promotion was measured using physical assessment, types of health problems, reflexes, OPD visiting history, DDST, immunization, feeding assessment, Infant death rate, etc. Maternal self-esteem, postpartum depression and family function were measured using the maternal self-report inventory(MRI), EPDS, and family apgar score(Fapgar), retrospectively. Result: All premature infants in the intervention group were in the normal range of growth and development, and the regular vaccination schedule. The health problems in the intervention group were addressed early so not to develop into adverse effects. The follow-up program for 6 months showed beneficial effects on MRI, EPDS, and Fapgar. Conclusion: A systemic follow-up health care program is beneficial on health promotion and risk reduction in 64 HRI including premature infants and their mothers.