We conducted a case-control study to examine the association between depression and Parkinson's disease (PD). Participants included 992 PD cases diagnosed after 2,000 and 279,958 individuals without PD from the NIH-AARP Diet and Health Study follow-up survey. Physician-diagnosed depression and PD were self-reported with information on the year of diagnosis in the following categories: before 1985, 1985-1994, 1995-1999, and 2000-present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR = 4.7, 95% CI = 3.9, 5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000 (OR = 2.0, 95% CI = 1.6, 2.4). This association was stronger for depression diagnosed in 1995-1999 (OR = 2.7, 95% CI = 2.0, 3.6), but was also noted for depression diagnosed in 1985-1994 (OR = 1.6, 95% CI = 1.1, 2.3) or even before 1985 (OR = 1.7, 95% CI = 1.3, 2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD.