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Objectives Major depression is associated with increased morbidity and mortality in vascular surgery patients. The US Preventive Services Task Force and American Heart Association recommend routine depression screening for adults, especially those with cardiovascular disease. Since routine depression screening has not been implemented in most vascular surgery clinics across the nation, we sought to determine the feasibility of depression screening and understand the prevalence and predictors of depression in patients presenting to a single institution’s vascular surgery clinic over a 4 month period. Methods From June to September 2020, vascular surgery clinic patients were administered a 26-item survey that included validated scales for depression (PHQ-9), pain, frailty, alcohol dependence, and nicotine dependence. Although not validated, the Rosenberg Self-Esteem Scale was also administered. Patient charts were reviewed for demographic information and medical history. 9-digit patient zip codes were used to determine Area Deprivation Index, a measure of socioeconomic status. Univariate and multivariate analyses were performed to understand the factors associated with increased depression prevalence in the study population. Results A total of 140 (36.4%) of 385 patients met study inclusion criteria. 35.7% of them screened positive for mild to severe depression (PHQ-9 scores ≥5). On univariate analysis, major depression was significantly associated with lower socioeconomic status ( p = 0.007), higher frailty ( p < 0.001), lower self-esteem ( p < 0.001), higher daily pain ( p < 0.001), health problems that interfere with social activities ( p < 0.001), fatigue ( p < 0.001), unmarried status ( p = 0.031), and lack of primary care provider ( p = 0.048). Multivariate analyses significantly predicted higher frailty (B= 0.487, p = 0.007) and lower self-esteem (B= −0.413, p < 0.001) in patients with depression. Depression was not associated with gender, age, employment status, smoking status, alcohol use, or type of vascular disease. Coclusions More than one-third of vascular surgery clinic patients have comorbid depression. Higher frailty and lower self-esteem are significant risk factors for depression. Prevention and early identification of frailty may improve outcomes. Depression screening in vascular surgery clinics is feasible and could be useful in determining which patients may benefit from more frequent follow-up and monitoring for associated comorbidities. Vascular surgeons may play an important role in screening for depression and referring patients for psychotherapy and/or pharmacotherapy.