Purpose To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment.Method A total of 312 AIS patients treated with bracing were enrolled in this study.The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up.The patients were divided into two groups according to the outcome of brace treatment (success/failure).The failure of brace treatment was defined as a curve progression of more than 5° compared to the initial Cobb angle or surgical intervention because of curve progression.Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor α (ERα), estrogen receptor β (ERfβ), tryptophan hydroxylase 1 (TPH-1), melatonin receptor 1B (MTNR1B) and matrillin-1 (MATN1), which were previously identified to be predisposition genes for AdS, were selected for genotyping by the PCR-RFLP method.Differences of genotype and allele distribution between the two groups were compared by the x2 test.A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment.Results There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group.Patients in the failure group were associated with the genotype GA (50.9 vs.17.9% p < 0.001) and the G allele (27.1 vs.12.0%, p < 0.001) at SNP rs9340799 of the ERα gene.Similarly, they were also associated with the genotype AT (33.3 vs.13.0%, p =0.002) and the A allele (16.7 vs.9.6%, p =0.033) at SNP rs10488682 of the TPH-1 gene.For MTNR1B, the difference of genotype distribution between the two groups was found to be statistically significant, while the difference of allele distribution between the two groups was found to be marginally statistically significant; for the MATN1 and ERβ genes, we found no significant differences of the genotype or allele distribution between the two groups.In the logistic regression analysis, ERα and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness.Conclusions ERα and TPH-1 might be potential genetic markers that could predict the outcome of brace treatment.Patients with the G allele at the rs9340799 site of the ERα gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.