Adherent–invasive Escherichia coli (AIEC) is a pathogen isolated from the ileum of patients with Crohn disease. IFNγ is a key mediator of immunity, which regulates inflammatory responses to microbial infections. Previously, we showed enterohemorrhagic E. coli prevents STAT1 activation. The aim of this study was to determine whether activation of STAT1 by IFNγ was prevented by AIEC infection, and to define the mechanisms used. Human epithelial cells were infected with three different AIEC strains or other pathogenic and commensal E. coli strains. Following infection, cells were stimulated with IFNγ, and STAT1 activation was monitored by immunoblotting. Our data show that live AIEC with active protein synthesis machinery is able to prevent IFNγ-mediated STAT1 phosphorylation, and that a secreted factor may be involved. We conclude that the suppression of epithelial cell STAT1 signal transduction by AIEC strains isolated from patients with Crohn disease represents a novel mechanism by which the pathogen evades host immune responses to the infection.