OBJECTIVE: To analyze the differences of risk factors on congenital heart defect (CHD)between floating population and permanent residents in Guangdong. METHODS: A multicenter case-control study was carried out to investigate the risk factors of CHD in floating population and in permanent residents. Data was from 34 Guangdong CHD Monitoring Network centers during the year of 2004 to 2011. Exposed information related to the parents at pre-pregnancy and early pregnancy periods, was collected, using the same questionnaire survey methodology in the two populations. Possible risk factors were analyzed by univariate analysis and multivariate non-conditional logistic regression(ENTER method)methods. Risk factors were compared between the two populations. RESULTS: Totally, 855 CHD cases and their controls from the floating population, as well as 1673 cases and their controls from the permanent residents were included in this study. Age of the children under study was defined from 28th week of gestation to 1 year old postnatal. In the floating population, specific risk factor for CHD appeared as:maternal passive smoking in early pregnancy, while the specific protective factor as high family income. However, the specific risk factors would include: having diseases as maternal diabetes mellitus or syphilis, living in a newly (within half a year) decorated house or with fetal macrosomia in the permanent residents. High education level showed as a risk factor in floating population, however contrarily, as protective factor to the permanent residents. Except for the factors related to having fever of the mother and infant with low birth weight, factors as having history of deliveries more than two, with maternal virus infection, exposure to chemical agent and negative bearing history etc., have higher OR values in floating population than in the permanent residents. CONCLUSION: Significant differences of risk factors for CHD were noticed between floating population and the permanent residents, which have their individual specific risk factors. Most of the ORs appeared higher in floating population than in the permanent residents.