Background: The potential benefits of hormone therapy (HT) in treating depressed postmenopausal women are controversial, and data on depression (re)emergence in the context of HT discontinuation are lacking. Objective: To determine whether HT is associated with a modified risk of new-onset depressive symptoms in elderly women. Method: Current depressive symptomatology was evaluated in 4,069 community-dwelling postmenopausal women aged 65 years and over who were randomly recruited from 3 French cities between 1999 and 2001. Depressive symptomatology was assessed using the Center for Epidemiologic Studies-Depression Scale at baseline and as part of the 2- and 4-year follow-up. Results: Over the follow-up period, multivariate logistic regression analyses adjusted for sociodemographic variables, measures of physical health, and cognitive impairment failed to find a significant association between HT at baseline and the incidence of depressive symptoms. However further analysis indicated an increased risk of incident depressive symptoms for women using transdermal estradiol treatment combined with synthetic progestin specifically (odds ratio [OR] = 1.59; 95% CI, 1.01-2.50; P = .046). In addition, while women taking HT continuously over the 4-year follow-up did not show an increased risk of depressive symptoms, women who stopped their treatment early after study inclusion, had a significantly higher risk (OR = 2.63; 95% CI, 1.52-4.55; P = .0005). Conclusions: Hormone therapy was not associated with a protective effect against the emergence of depressive symptoms in elderly postmenopausal women. However, discontinuing treatment could increase the risk of depressive symptoms. Data on the appropriate management of depression in the context of HT discontinuation among postmenopausal women require further investigation.