Patients with greater adiposity before lung transplantation are at an increased risk for worse post-transplant outcomes. Few studies have addressed whether pre-transplant weight loss mitigates this risk. In this study we examined the association between pre-transplant weight loss and post-transplant clinical outcomes. We conducted a retrospective cohort study of patients who received a lung transplant at the Duke University Hospital from May 1, 2005 to April 30, 2015. The sample included adult transplant recipients with restrictive, obstructive, and vascular diseases. Cox proportional hazards models were used to examine mortality and chronic lung allograft dysfunction (CLAD)-free survival, and negative binomial regression analyses were used to examine length of stay (LOS). Weight loss was assessed from change in body mass index (BMI). The cohort consisted of 810 patients. Initially, 403 (50%) were overweight and 109 (13%) were obese by BMI criteria. Greater pre-transplant weight loss was associated with dose-response improvements in survival (hazard ratio [HR] 0.83 [0.72 to 0.97], p = 0.018), with modest (0% to 3%, HR 0.91), moderate (7% to 10%, HR 0.83), and high (>15%, HR 0.71) levels of weight loss conferring longer survival, independent of initial weight (p = 0.533 for interaction). Weight loss was also associated with improved CLAD-free survival (HR 0.84 [0.71 to 0.99], p = 0.034) and shorter LOS (b = ‒0.17, p < 0.001). Weight loss before transplantation was associated with improved short- and long-term clinical outcomes, independent of initial weight. Survival improved proportionally to percentage of weight lost. The mechanisms by which weight loss improve clinical outcomes warrant further exploration.