Abstract: Objective　To explore the relationship between endothelin-1 (ET-1) +138A/- gene polymorphism and vasovagal syncope (VVS) in children. Method　The head-up tilt test (HUT) was performed in children with unexplained syncope. Eighty HUT-positive and VVS-diagnosed patients were assigned to the VVS group, and were further divided into three clinical subgroups: mixed-response type, cardioinhibitory-response type and vasodepressor-response type. Eighty HUT negative patients were assigned to the HUT-negative group. Another 80 healthy children were selected as normal control group. The clinical characteristics of children in VVS group and HUT-negative group were collected and venous blood samples were taken from all participants in three groups. ET-1+138A/- gene polymorphism was detected by high-resolution melting curve and polymerase chain reaction sequencing. The genotype and allele frequency were analyzed and compared between different groups and VVS subgroups. Results　Compared with HUT negative group, the proportion of girls in VVS group was higher, and there was statistical difference (P<0.05). There was no difference in the distribution of +138A/- genotypes (3A3A, 3A4A, 4A4A) and allele (3A, 4A) frequencies among normal control group, HUT negative group and VVS group (P>0.05). There were statistically differences in the distribution of +138A/- genotypes and allele frequencies among the clinical subgroups of VVS (mixed-response type, cardioinhibitory-response type and vasodepressor-response type) (P<0.05). The frequencies of 3A4A genotypes and 4A alleles in vasodepressor-response type subgroup were higher than those in other clinical subgroups (P<0.05). Conclusion　ET1+138A/- gene polymorphism was not found to be associated with VVS in children, but the frequencies of 3A4A genotype and 4A allele were higher in vasodepressor-response type, suggesting that this gene locus may be involved in the regulation of blood pressure during VVS attack.