Gender disparities, particularly among young women with cardiovascular disease, are a growing cause for concern. Depression is a prevalent and prognostically important comorbidity in peripheral arterial disease (PAD), but its prevalence has not been described as a function of gender and age. Therefore, we compared depressive symptoms at the time of PAD diagnosis and 6 months later by gender and age in PAD patients. The study enrolled 444 newly diagnosed patients with PAD (32% women) from two Dutch vascular outpatient clinics. Patients' depressive symptoms were assessed with the 10-item Center for Epidemiological Studies Depression Scale (CES-D) at baseline and 6 months later (CES-D scores >or=4 indicate significant depressive symptoms). Logistic regression models were constructed to evaluate the relationship among four gender-age groups (women <65 and >or=65 years; men <65 and >or=65 years [reference category]) and baseline and 6-month follow-up depressive symptoms. Initially, 33% of women <65 years had significant depressive symptoms, and 6 months later, significant depressive symptoms had developed in 19% of the other younger women. These rates were much higher than other gender-age groups (range at baseline, 11%-16%; 6-month incidence, 6%-10%; P or=65 years, whereas other gender-age groups were not at risk. Additional adjustment for change in the ankle-brachial index did not explain the increased depression risk in younger women (OR, 3.5; 95% CI, 1.2-10.2). Significant depressive symptoms are more common in younger women with PAD than in other gender-age groups, both at the time of diagnosis and 6 months later. To eradicate gender-based disparities in PAD, depression screening and monitoring in younger women may be an important direction for future research and intervention.