Background: One indicator of a country's progress is the infant mortality rate. Infant mortality is affected by many factors, both exogenous and endogenous. This study aimed to determine the factors causing significant infant mortality to reduce infant mortality in Karanganyar Regency. Subjects and Method: This study was an observational study with a cross-sectional design. This study was conducted in Karanganyar, Central Java, from February to May 2020. A sample was 200 infants aged 1-11 months were selected by fixed disease sampling. The variables observed for the effect were infant mortality, clean and healthy life behavior, exclusive breastfeeding, parental income, maternal education, infant nutritional intake, immunization status, birth weight of infants, illness history of infants, health services, and house sanitation. The data were collected by questionnaire and analyzed using path analysis with Stata 13. Results: The risk of infant mortality increased by the cleanliness of the home environment (b=3.84; 95%CI=1.76 to 5.92; p<0.001), infant nutrition intake (b=4.07; 95 CI=2.25 to 5.89; p<0.001), illness history of infants (b=3.03; 95% CI= 1.34 to 4.72; p<0.001). The risk of infant mortality decreased by clean and healthy life behavior (b= -5.34; 95%CI=-7.75 to -2.94; p <0.001). Infant mortality was affected indirectly by exclusive breastfeeding, parental income, maternal education, birth weight of infants, immunization status, and health care facilities.
Conclusion:Infant mortality is directly affected by the cleanliness of the home environment, clean and healthy life behavior, nutritional intake of infants, and illness history of infants. Infant mortality is indirectly affected by exclusive breastfeeding, parental income, maternal education, birth weight of infants, immunization status, and health care facilities.