This meta-analysis aimed to analyze the association between CD14 C-159T and C-260T polymorphisms and periodontitis risks because previous results have been conflicting. We used 12 eligible case-control studies involving 1435 cases and 1446 controls to evaluate this association. Compared with the common CD14 C-159T and C-260T genotypes, there was no significant association of T alleles and the CT/TT genotypes polymorphism with periodontitis risk (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.83-1.27 for C vs. T; OR, 1.07; 95% CI, 0.83-1.38 for CT/TT vs. CC). A similar result was found in a subgroup analysis by ethnicity and periodontitis type. An enhanced risk for periodontitis was demonstrated in the comparison of subjects carrying the CT genotype versus CC homozygotes (overall OR, 1.681; 95% CI, 1.048-2.695; P for heterogeneity=0.367; I2=2.00%) for the C-260T genotype. Our meta-analysis revealed that the 2 common CD14 polymorphisms, C-159T and C-260T, have no association with the likelihood of periodontitis. In subgroup analysis by ethnicity and periodontitis type, the results also did not show any association. The effect of genetic networks and their mutual interactions in the CD14 signaling pathway on susceptibility to periodontitis need to be studied further.