The purpose of this investigation was to assess the effect of empirical antibiotic treatment on 30-day mortality among debilitated inpatients with dementia and Gram-negative bacteremia. A retrospective cohort study in the years 2005-2007 was undertaken. Data were collected through patient chart review. The association between individual variables and 30-day mortality was assessed through univariate analysis. Variables significantly associated with mortality (p < 0.05) were entered into a logistic regression analysis. Adjusted odds ratios (ORs) for mortality with 95% confidence intervals (CIs) are shown. Subgroup analysis of patients with and without decubitus ulcers was performed. In our cohort of 378 patients with dementia and Gram-negative bacteremia, the 30-day mortality was 39% overall and 61% in the subgroup of patients with decubitus ulcers. Inappropriate empirical therapy was associated with higher mortality, although this effect was not statistically significant (OR 1.41, 95% CI 0.86-2.29). Inappropriate empirical therapy did not affect mortality in the subgroup of patients with decubitus ulcers (OR 0.37, 95% CI 0.11-1.28). Other factors found to independently affect mortality included age, co-morbidities, source of infection, sepsis severity, and hospital-acquired infection. Appropriate empirical antibiotic therapy for patients with dementia and severe bacterial infection did not have a clear advantage, especially in the sickest group of patients with decubitus ulcers.