People with diabetic foot ulcers report poor quality of life. However, prospective studies that chart quality of life from the onset of diabetic foot ulcers are lacking. We describe change in quality of life in a cohort of people with diabetes and their first foot ulcer during 18 months and its association with adverse outcomes. In this prospective cohort study of adults with their first diabetic foot ulcer, the main outcome was change in Medical Outcomes Study 36-Item Short Form Health Survey scores between baseline and 18-month follow-up. We recorded baseline demographics, diabetes characteristics, depression, and diabetic foot outcomes and mortality at 18 months. In 253 people with diabetes and their first ulcer, there were 40 deaths (15.8%), 36 amputations (15.5%), 99 recurrences (43.2%), and 52 nonhealing ulcers (21.9%). The 36-Item Short Form Health Survey response rate of survivors at 18 months was 78% (n = 157). There was a 5- to 6-point deterioration in mental component summary scores in people who did not heal (adjusted mean difference, -6.54; 95% confidence interval, -12.64 to -0.44) or had recurrent ulcers (adjusted mean difference, -5.30; 95% confidence interval, -9.87 to -0.73) and a nonsignificant reduction in those amputated (adjusted mean difference, -5.00; 95% confidence interval, -11.15 to 1.14). Quality of life deteriorates in people with diabetes whose first foot ulcer recurs or does not heal within 18 months.