External apical root resorption (EARR) is a frequent iatrogenic problem following orthodontic treatment in endodontically-treated teeth, about which the literature reports substantial variability in post-orthodontic treatment EARR responses. The main focus of the present study is to clarify whether variants in the interleukin-1 receptor antagonist gene coding for the IL-1ra protein have a positive/negative influence on EARR of endodontically-treated teeth. Ninety-three orthodontic patients were genetically screened for a single nucleotide polymorphism (SNP:rs419598) in the IL1 cluster. The sample was classified into 2 groups: group 1 (affected-group) showed radiographic EARR of more than 2mm; group 2 (control-group), had no EARR or EARR ≤ to 2mm following orthodontic treatment on root-filled teeth. Logistic regression analysis was performed to obtain an adjusted estimate between the SNPs studied and EARR. Genotype distributions, allelic frequencies, adjusted odds ratios (OR) and 95% confidence intervals were also calculated. We found that subjects homozygous [1/1(TT)] for the IL1RN gene [OR:10.85; p=0.001;CI:95%] were at risk of EARR in root-filled teeth. Genetic variants in the antagonist axis balance of the IL1RN (rs419598) have a direct repercussion on the predisposition to post-orthodontic EARR in root-filled teeth. Variants in allele 1 of the interleukin-1 receptor antagonist gene(rs419598) are associated(p=0.001**) with an increased risk of suffering post-orthodontic EARR in root-filled teeth.