Summary: To identify the factors contributing to birth defects using 18-year data for better intervention planning. Materials and Methods: A retrospective study was carried out using data collected from 169,155 perinatal infants at the city hospital of Zhangye from January 1996 to January 2012. Results: Among the infants, 289 had birth defects. Of them, 182 were detected before the birth with the incidence of 1.71‰ and detection rate of 62.98%; the perinatal mortality was 5.42%, while the mortality of defect infant was 175.42%. The most common defects were congenital heart disease, multiple finger (toe), cheiloschisis combined with palatochisis, and ear abnormalities. Univalent conditional logistic regression analysis showed that there were eight statistically significant risk maternal factors contributing to the birth defects, including fever, viral infection, gestational diabetes mellitus, hypertension, other disease, antibiotics, other drugs, and pesticide exposure in early pregnancy. Multivariate logistic regression analysis showed that exposure to pesticides (OR = 14. 43), viral infection (OR = 7. 65), the use of other drugs (OR = 6. 69), and antibiotics (OR = 6. 55) were associated with the birth defects. Conclusion: It is clear that the birth defects can be reduced by taking precautionary measures before and during pregnancy, by prenatal diagnosis, and by proper treatment of the children with defects.