Thirty-four Escherichia coli isolates from 91 ready-to-eat lettuce packages, obtained from local supermarkets in Northern California, were genotyped by multilocus sequence typing, tested for susceptibility to antimicrobial agents, and screened for b-lactamase genes. We found 15 distinct sequence types (STs). Six of these genotypes (ST1198, ST2625, ST2432, ST2819, ST4600, and ST5143) have been reported as pathogens found in human samples. Twenty-six (76%) E. coli isolates were resistant to ampicillin, 17 (50%) to ampicillin/sulbactam, 8 (23%) to cefoxitin, and 7 (20%) to cefuroxime. bla CTX-M was the most prevalent b-lactamase gene, identified in eight (23%) isolates. We identified a class A broad-spectrum b-lactamase SED-1 gene, bla SED , reported by others in Citrobacter sedlakii isolated from bile of a patient. This study found that fresh lettuce carries b-lactam drug-resistant E. coli, which might serve as a reservoir for drug-resistance genes that could potentially be transmitted to pathogens that cause human infections.