Early childhood caries (ECC) affects children all over the world and has high prevalence and severity in preschool children. Different social, biological and behavioral factors compose a network of causal factors for ECC. The aim was to evaluate the association between socioeconomic variables and caries at baseline, and the presence of Streptococcus mutans and Lactobacillus spp. microorganisms with the progression of caries lesions after two years of follow-up in a group of children. At baseline, 163 children (3-4 years old) living in the areas of 12 primary care services of the Hospital Group Conceição (GHC, Porto Alegre, RS, Brazil) were evaluated. After two years, 119 children were re-evaluated. Clinical examinations were conducted by calibrated examiners using the ICDAS criteria. A sociodemographic questionnaire was applied to the children's parents and saliva samples were collected from the children for microbiological analysis. Descriptive statistics and multivariate Poisson regression analysis were performed in the statistical analysis. The factors associated with the caries progression were marital status of mothers (p=0.040), higher S. mutans counts (p=0.031) and the presence of cavitated lesions at baseline (p<0.001). The caries lesions progression in preschool children enrolled in primary health care was directly associated with marital status, presence of cavitated lesions at baseline and higher S. mutans counts at two-year follow-up.