Background.Two polymorphisms in the macrophage migration inhibitory factor (MIF) gene have been associated with inflammatory diseases (-794 CATT5-8 and -173G>C); however, so far there are no reports of studies related to oral health. Objectives.To genotype the -794 CATT5-8 and -173G>C MIF polymorphisms in Mexican patients with apical periodontitis as a genetic risk of exacerbation. Material and methods.The study involved 120 patients with apical periodontitis: 60 with a diagnosis of acute apical periodontitis (Group A) and 60 without previous episodes of exacerbation (Group B).Allelic discrimination was performed from peripheral blood DNA; the repeat polymorphism -794 CATT5-8 was genotyped with sequencing, while the -173G>C polymorphism was determined using real-time polymerase chain reaction (RT-PCR) using TaqMan probes.The associations between MIF polymorphisms, haplotypes and the risk of exacerbated apical periodontitis were assessed.Results.The allele CATT7 was associated with the risk of a stage of acute inflammation (OR = 4.13; 95% CI = 1.82-9.63;p =< 0.001).Regarding the -173G >C polymorphism, a process of inflammation exacerbation was only associated with the CC genotype (OR = 4.1; 95% CI = 1.02-20.84;p = 0.045).The analysis of the haplotype showed that the combination CATT7/C increases the risk of exacerbation of apical periodontitis (OR = 3.57; 95% CI = 1.038-13.300;p = 0.021). Conclusions.The polymorphisms -794 CATT5-8 and -173G>C MIF seem to significantly influence the development of a state of exacerbated inflammation in patients with apical periodontitis.