A variety of equations are used to estimate glomerular filtration rate (eGFR). These formulas have never been validated in the setting of traumatic amputation. In this retrospective study involving 255 military personnel with traumatic amputations at a single outpatient center, muscle mass lost was estimated using percentage of estimated body weight lost (% EBWL). Serum creatinine (Scr) and eGFR by the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were compared to % EBWL for each patient. The average Scr for the group studied was also compared with a cohort matched for age, sex, and race from the Third National Health and Nutrition Examination Survey (NHANES III). Percentage EBWL correlated significantly with Scr (R2 = 0.095, p < 0.0001), eGFR by MDRD (R2 = 0.077, p < 0.0001), and eGFR by CKD-EPI (R2 = 0.074, p < 0.0001). The average Scr was significantly lower than a similar population from NHANES III (0.83 +/- 0.137 mg/dL vs. 1.14 +/- 0.127 mg/dL, p < 0.0001). Percentage EBWL has a significant correlation with Scr and eGFR by both the MDRD and CKD-EPI equations. Furthermore, patients with traumatic amputation have significantly lower Scr values than the general population. Creatinine-based estimators of GFR may overestimate renal function in the setting of traumatic amputation.