This study is conducted to investigate the association between major depressive disorder and the subsequent development of Alzheimer disease (AD) in elderly patients with different health statuses using Taiwan's National Health Insurance Research Database (NHIRD).A retrospective cohort study was performed on subjects over 65 years old from 2002 to 2006 using a random sampling from the 1 million beneficiaries enrolled in the NHI. Patients who were diagnosed with major depressive disorder were selected as the case group. Subjects in the control group were selected from elderly patients who did not have depression during the study period by matching age, sex, and index date of depression with subjects in the case group using a ratio of 1:4 (case:control). Both groups of patients were checked annually over a period of 7 years to observe whether they subsequently developed AD.A total of 1776 subjects were included in the case group while 7104 subjects were in the control group. After the follow-up period, 59 patients (3.3%) with depression developed AD while 96 patients (1.4%) without depression developed AD. The Kaplan-Meier curves showed that the incidence rate of AD in both groups varied significantly depending on different health statuses (log-rank P < .001). Results of the generalized estimating equation model found that patients with depression (hazard ratio [HR] = 1.898; 95% confidence interval [CI] = 1.451-2.438), very severe health status (HR = 1.630; 95% CI = 1.220-2.177), or artery diseases (HR = 1.692; 95% CI = 1.108-2.584) were at a higher risk of developing AD than other groups.The association between major depressive disorder and the later development of AD varied depending on the health statuses of elderly patients. Clinicians should exercise caution when diagnosing and treating underlying diseases in elderly depressed patients, and then attempt to improve their health status to reduce the incidence rate of subsequent AD development.