Background: Infection is a major health problem in orphanage centers and represents a major cause of morbidity and mortality among residents. Health education is an essential component of infection control and should be offered to all children and their caregivers. The aim of current study: to evaluate the effect of a health education program about infection control on practice of caregivers & on infection rates in Mygoma orphanage center. Materials and methods: An Intervention study (Quasi-experimental: pre and posttest design for the same group). The study was conducted in Mygoma orphanage center in Khartoum state. The study sample consisted of 92 caregivers. Data were collected using a checklist to measure practice and laboratory investigations. The intervention program included infection control lectures, handouts, posters, and attention to environmental cleaning and disinfection. Compliance with these measures was monitored and recorded. Data were analyzed using Statistical Packages for Social Sciences (SPSS). Results: the study showed significant differences were found regarding correct practices between the pretest and posttest (P < 0.05) also the study revealed that, the swab for culture and sensitivity, in food table the isolated organisms were staph 23.1%, E coli 7.7%, Protus 7.7%, Bacillus 7.7%. and klebseilla 15.4% at pretest investigation, while at posttest the isolated organisms were staph 15.4%, and klebseilla 7.7%. In diapering table, the isolated organisms were staph 15.4%, E coli 30.7%, Protus 7.7%, klebseilla 15.4% and Pseudomonas 7.7% at pretest investigation, while at posttest measurement the isolated organisms were E coli 15.4% and klebseilla 7.7%. Conclusion: The study concluded that educational and environmental infection control program had a significant impact related to the improvement of the caregiver's practice skills and decrease in infection rates post application of the program.