Toxigenic Vibrio cholerae serogroup O141 has been associated with sporadic cholera-like diarrhea and bloodstream infection in the United States. Consumption of seafood and proximity to the coast may increase the risk of infection. All V. cholerae isolates recovered from stool samples of patients with diarrhea or from a normally sterile site should be serogrouped and assessed for cholera toxin production. Improved surveillance and case-control studies are needed to further characterize illness and risk factors for V. cholerae O141 infection.