BACKGROUND: We examined the prevalence of comorbid medical illnesses in Alzheimer's disease (AD) patients at different severity levels. We also examined the effect of cumulative medical comorbidity on cognition and function. METHODS: Analyses of data from 679 AD patients (Mini-Mental State Exam score range 0-30, mean +/- SD = 11.8 +/- 8) from 13 sites (four dementia centers assessing outpatients, four managed care organizations, two assisted living facilities, and three nursing homes) prospectively recruited using a stratification approach including dementia severity and care setting. Medical comorbidity was quantified using the Cumulative Illness Rating Scale-Geriatric. RESULTS: Across patients, 61% had three or more comorbid medical illnesses. Adjusting for age, gender, race, and care setting, medical comorbidity increased with dementia severity (mild to moderate, p <.01; moderate to severe, p <.001). Adjusting for age, educational level, gender, race, and care setting, higher medical comorbidity was associated with greater impairment in cognition (p <.001) and in self-care (p <.001). CONCLUSIONS: Despite the limitation of a cross-sectional design, our initial findings suggest that there is a strong association between medical comorbidity and cognitive status in AD. Optimal management of medical illnesses may offer potential to improve cognition in AD.