This study addresses the potential association of Escherichia coli O157:H7 genetic clusters with severe clinical manifestations in humans. The genotypes used in this model-based clustering had been delineated on the basis of lineage-specific polymorphism assay, Shiga toxin-encoding bacteriophage insertion site assay, clade typing, tir (A255T) polymorphism, variant analysis of Shiga toxin 2 gene, and antiterminator Q genes. Based on this model, the distribution of genotypes among tested strains suggested the presence of 6 main genetic clusters of E. coli O157:H7 strains. Clusters 1 and 3 were observed to be more frequent among E. coli O157:H7 strains isolated from bloody diarrhea and hemolytic uremic syndrome, respectively. Consequently, our findings supported the growing evidence of the existence of distinct genotypes of E. coli O157:H7 that differ in their virulence levels to human.