We have estimated the excess risk of HUS and RRT attributable to stx2a-only E. coli O157:H7, relative to the stx1a2a genotype, demonstrating the population-level implications of the purported attenuation of stx2a virulence by stx1a. If stx2a-only strains had replaced stx1a2a strains in our population, we would have observed >25% more HUS cases. The gene discussed is STX1A; the disease is hemolytic-uremic syndrome.