Abstract: Vesicoureteral reflux (VUR) is a common childhood problem, causing renal wounds and escalating the risk of renal deficiency and hypertension. A vast literature exists suggesting that genetic variations play a significant role in the pathogenesis of VUR. The aim of the present study was to estimate whether genetic polymorphisms of IL-19 (GC rs2243158, AT rs2243158) and IL-20 (AG rs2981573, TG rs2981572) genes are involved in the development of VUR. Materials and methods: The tetra amplification mutation refractory system-polymerase chain reaction (Tetra-ARMS PCR) was applied for analyzing four polymorphic sites of IL-19 (GC rs2243158, AT rs2243158) and IL-20 (AG rs2981573, TG rs2981572) genes in 110 healthy controls and 124 VUR children. Results: A significant association was found between the combined genotypes of IL19GC + CC and IL20TG + GG and increased risk of VUR (OR=1.90, 95% CL, 1.06–3.41; OR=1.87, 95% CL, 1.06–3.29, respectively). The frequency of allele G in both sites of IL-20 (IL20AG rs2981573 and IL20TG, rs2981572) showed a statistically significant difference (p =0.01) between cases and controls in comparison with the wild type. The combined haplotype analysis of IL-19 and IL-20 polymorphic sites revealed that HT2, HT3 and HT5 haplotypes marginally increased the risk of VUR, but not statistically significantly. Gene–gene interaction data of IL-19 (GC rs2243158, AT rs2243158) and IL-20 (AG rs2981573, TG rs2981572) in various genotype patterns highlighted the fact that most of the genotype combinations increased the risk of disease insignificantly. Conclusion: This is the first evidence regarding IL-19 and IL-20 cytokine genes polymorphism and risk of VUR, suggesting the need for further study with large sample size and in different populations to confirm the presented data. [Copyright &y& Elsevier]