The aim of this study is to investigate the clinical features and drug sensitivity of elderly patients with bloodstream infection by Escherichia coli (E. coli) . The medical records of 340 elderly patients with E. coli infection in The Affiliated Hospital of Xuzhou Medical University from January 2013 to December 2016 were retrospectively analyzed. SPSS software was used for analysis. The results showed that the patients were all associated with underlying diseases (malignant diseases, hypertension, diabetes, lung infections, etc.). The main routes of infection were digestive tract (38.5%), respiratory tract (36.8%) and urinary tract (22.6%). Extended-spectrum β-lactamase (ESBL)-producing E. coli strains were detected in 96 cases (28.2%). The isolated strains were mostly resistant to ampicillin, chemitrim ciprofloxacin, piperacillin, the 3rd generation of cephalosporins, and levofloxacin, but were sensitive to carbapenems.