This cross-sectional study was conducted to identify the association between two key microorganisms ~i(S. mutans~i and ~iLactobacilli)~i and dental caries among the first grade primary school children in Songkla, Thailand. A total of 363 children were examined for microbiology and dental caries status. Potential confounders including socioeconomics status, parents education and childrens oral health behaviors were assessed by interviewing their parents The results revealed that this group had high prevalence (99.2%) and high severity of dental caries experience (mean deft=9.07(+,-)3.44 and mean DMFT =0.89(+,-)1.25). Prevalence of high levels of ~iS. mutans~i (>10(6) CFU/ml) and ~iLactobacilli~i (>10(5) CFU/ml) were 50% and 30% respectively. Multiple logistic regression models of both dentitions showed that those children who had high level of ~iS. mutans~i (>10(6) CFU/ml) had higher risk to develop dental caries than those who had low level (<10(6) CFU/ml)(OR=2.18 with 95%CI=1.38-3.52) after adjusting for frequency of tooth brushing and parents education. While Log. ~iLactobacilli~i was significantly associated with risk of dental caries, risk was not as strong as ~iS. mutans~i (OR=1.12 with 95%CI=1.02-1.23). Oral health behaviors as well as parents education were significantly associated with risk of dental caries. Children who brushed their teeth every day had lower caries experience than those children who did not. Also, children whose parents completed higher education than primary school level had low number of caries teeth. It is concluded that these two microorganisms are responsible for caries status in children of this age group after adjusting for socioeconomic status, parents education and oral health behavior. The study also demonstrated that this microbiological method is feasible in field study and could identify children with high risk of dental caries, thus a special curative and preventive oral health program should be provided.