Escherichia coli isolates from 3 consecutively encountered patients with serious, invasive, non-urinary tract extraintestinal infections (pneumonia, deep surgical wound infection, and vertebral osteomyelitis with associated epidural/psoas/iliacus abscesses) were characterized, using molecular methods, as to extended virulence genotype and phylogenetic background. All 3 isolates exhibited virulence genotypes and genomic profiles characteristic of specific familiar virulent clones of extraintestinal pathogenic E. coli (ExPEC), which traditionally have been regarded primarily as uropathogenic or as associated with meningitis. These included E. coli O1/O2:K1:H7, E. coli O18:K1:H7, and a recently described E. coli O11/O17/O77:K52:H18 clonal group (clonal group A). These findings demonstrate the extraintestinal pathogenic versatility of ExPEC clones, which supports the use of an inclusive designation for such strains and suggests the possibility of cross-syndrome protective interventions. They also provide novel evidence that multidrug-resistant epidemic clonal group A can cause extraintestinal infections other than uncomplicated urinary tract infections and can cause them in hosts other than young women.