Abstract-Little is known about the relationship between lower-limb amputation (LLA) and subsequent changes in body weight. We conducted a retrospective cohort study using clinical and administrative databases to identify and follow weight changes in 759 males with amputation (partial foot amputation [PFA], n = 396; transtibial amputation [TTA], n = 267; and transfemoral amputation [TFA], n = 96) and 3,790 men without amputation frequency-matched (5:1) on age, body mass index, diabetes, and calendar year from eight Department of Veterans Affairs medical care facilities in the Pacific Northwest. We estimated and compared longitudinal percent weight change from baseline up to 39 mo of follow-up in men with and without amputation. Weight gain in the 2 yr after amputation was significantly more in men with an amputation than without, and in men with a TTA or TFA (8%-9% increase) than in men with a PFA (3%-6% increase). Generally, percent weight gain peaked at 2 yr and was followed by some weight loss in the third year. These findings indicate that LLA is often followed by clinically important weight gain. Future studies are needed to better understand the reasons for weight gain and to identify intervention strategies to prevent excess weight gain and the deleterious consequences that may ensue.