Background: When managing patients with disorders that require clinical intervention, a practical assessment of body habitus is valued. The Duffull-Green lean body weight (LBW) equation was derived and validated in adults across a wide body mass index (BMI) range. Whether this predictive equation will perform well in patients at BMI extremes or perform better than a widely used empiric “ideal” body weight (IBW) equation is unknown. Materials and Methods: Calculated LBW and calculated IBW were each compared with the dual-energy x-ray absorptiometry (DXA)–derived lean body mass (LBM) by simple linear regression. A mixed model was used to determine how well the LBW equation performed over time in patients with more than 1 DXA measurement. Results: At time 0, 32 patients were 18–67 years old, and all were obese (BMI: 36–65 kg/m2), while the remaining 7 had parenteral nutrition–dependent intestinal failure (BMI: 17–25 kg/m2). A subset of patients underwent bariatric surgery after time 0 (BMI at follow-up: 22–49 kg/m2). The LBW equation was a predictor of LBM (R2 = 0.67, P < .0001), while the IBW equation was not (R2 = 0.04, P = .25). The LBW equation remained a predictor of LBM over time (P < .0001) without significant interaction by number of months since time 0. Conclusion: The Duffull-Green LBW equation successfully predicted lean body mass in a patient population with a wide range of BMIs at both a single point in time and after considerable weight loss. In the clinical setting, an equation that performs well in various disease states and body sizes is advantageous.