Shiga toxin (Stx)–producing Escherichia coli (STEC) from patients with hemolytic-uremic syndrome (HUS), patients with diarrhea without HUS, or asymptomatic subjects were genotyped to assess associations between stx₂ variants and clinical manifestations of infection. Neither stx_2d nor stx_2e was found in 268 STEC isolates from patients with HUS. Of 262 STEC isolates from patients with diarrhea, stx_2d was found in 41 (15.6%; P<\,.000001), and stx_2e was found in 12 (4.6%; P= .0004). The stx_2c genotype frequency was similar among isolates from patients with HUS (3.7%) and diarrhea (5.0%). The frequencies of stx_2c, stx_2d and stx_2e among 96 STEC isolates from asymptomatic subjects were comparable to those among isolates from patients with diarrhea. None of the 626 STEC isolates contained stx_2f. All stx_2d-positive or stx_2e-positive STEC isolates were eae negative and originated from subjects older than those with STEC isolates with stx_2c. stx_2c-positive STEC isolates can cause HUS, but the presence of stx_2d or stx_2e may predict a milder disease with a minimal risk of HUS