OBJECTIVES To study potential differences in the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis with and without diabetes mellitus. DESIGN Retrospective review of medical records. SETTING University hospital. PARTICIPANTS Eighty-eight patients aged 65 and older with diabetes mellitus (DM) (57 female; 64.8%) and 118 controls without DM (75 female; 63.6%), matched for age and sex, hospitalized with acute pyelonephritis between January 1997 and December 2005. MEASUREMENTS Medical records were reviewed for demographic, clinical, and microbiological characteristics. RESULTS The median age of both groups was 74 (range 65-95). Twenty-seven people with DM (30.7%) and 13 controls (11.0%) had bacteremia (P=.001). People with DM had longer fever (median 4.5 vs 2.5 days; P <.001), longer hospitalization (median 10 vs 7 days; P <.001), and greater mortality (12.5% vs 2.5%; P <.01) than controls. Logistic regression analysis proved DM to be an independent predictor of bacteremia, long hospitalization, and mortality. Escherichia coli was the most common microorganism found in both groups, whereas Candida spp. were implicated more frequently in people with DM than controls (12.7% vs 1.7%; P <.01). Antimicrobial resistance did not increase over the study period. CONCLUSION Acute pyelonephritis in elderly people with DM is associated with risk of bacteremia, long hospitalization, and mortality.