OBJECTIVE - The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer. RESEARCH DESIGN AND METHODS - A prospective cohort design was used. Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London, U.K. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM (Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders. Potential covariates were age, sex, marital status, socioeconomic status, smoking, antidepressant use, AlC, macro- and microvascular complications, and University of Texas classification-based severity and size of ulcer. The main outcome was mortality 18 months later, and AlC was the secondary outcome. The proportion who had an amputation, had recurrence, and whose ulcer had healed was recorded. RESULTS - A total of 253 people with their first diabetic foot ulcer were recruited. The prevalence of minor and major depressive disorder was 8.1% (n = 21) and 24.1% (n = 61), respectively. There were 40 (15.8%) deaths, 36 (15.5%) amputations, and 99 (43.2%) recurrences. In the adjusted Cox regression analysis, minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression (3.23 [95% CI 1.39-7.511 and 2.73 [1.38-5.401, respectively). There was no association between minor and major depression compared with no depression and AlC (P = 0.86 and P 0.43, respectively). CONCLUSIONS - One-third of people with their first diabetic foot ulcer suffer from clinical depression, and this is associated with increased mortality