Objective-Because depressive symptoms are prevalent among patients with peripheral arterial disease (PAD), our goal was to study the effect of depressive symptoms over time on functional decline among patients with PAD.Methods-We conducted a prospective cohort study of 417 patients with PAD followed annually for 2 years. A Geriatric Depression Scale Short Form (GDS-S) score >5 was considered positive for depressive symptoms. Depressive symptom categories based on annual GDS-S measures included persistent, new, resolved, and no depressive symptoms. Outcome variables were change in 6-minute walk distance, 4-meter fast walking velocity, and short physical performance battery (0-12 scale, 12 = best). Results are adjusted for age, sex, race, body mass index, marital status, exercise level, smoking, ankle brachial index, leg symptoms, comorbidities, beta-blocker medication use, antidepressant medications, and interim medical events.Results-In adjusted analyses, patients with new depressive symptoms had greater annual decline in fast walking velocity compared with that of patients with no depressive symptoms (−0.08 versus −0.01 meters/second per year, p = .02). Patients with persistent depressive symptoms had greater annual decline in 6-minute walk distance (−86.4 versus −41.5 feet/yr, p = .04), fast walking velocity (−0.08 versus −0.01 meters/second per year, p = .004), and short physical performance battery (−0.73 versus −0.18 per year, p = .005) compared with that of patients with no depressive symptoms.Conclusions-Among patients with PAD, persistent and new depressive symptoms are associated with greater annual decline in functional performance. Further study is needed to determine the mechanisms of these associations and whether treatment of depressive symptoms prevents functional decline in persons with PAD.