The basis for vesicoureteral reflux (VUR) is considered to be primarily genetic, with a 30-50% incidence of VUR in first-degree relatives of patients. The search for the causative gene or genes has been elusive, likely because of VUR being genetically heterogeneous with complex inheritance patterns. In this study, a genome-wide analysis of VUR with high-density single nucleotide polymorphisms was conducted with the aim of identifying susceptibility loci for VUR in 98 families with two or more affected children. Using the affected sib-pair method of analysis in 150 sib-pairs, we identified a genome-wide statistically significant linkage peak with an LOD score greater than 4 on chromosome 5 and two linkage peaks with LOD scores greater than 3.6 on chromosomes 13 and 18 were identified in these 98 families. These results suggested that multiple genes are likely to contribute to the formation of VUR phenotype. Further mapping of these linkage peaks may help identify the causative genes.