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Background Obesity after traumatic brain injury (TBI) is a public health issue and no evidence-based weight loss interventions exist to meet the unique needs of individuals after TBI. Purpose To (a) examine the efficacy of the Diabetes Prevention Program Group Lifestyle Balance for TBI (GLB-TBI) weight-loss intervention compared to an attention control for primary (weight-loss) and secondary health outcomes; (b) determine participant compliance with the GLB-TBI; and (c) determine if compliance is associated with improved outcomes. Methods Individuals with moderate to severe TBI, age 18–64 years, ≥6 months postinjury, and body mass index of ≥25 kg/m2 were randomized to a 12-month, 22-session GLB-TBI intervention or attention control condition. Weight-loss (lbs.), anthropometric, biomarkers, and patient-reported outcomes were collected at baseline, 3, 6, and 12 months. Results The GLB-TBI group (n = 27) lost 17.8 ± 41.4lbs (7.9%) over the 12-month program and the attention control group (n = 27) lost 0 ± 55.4lbs (0%). The GLB-TBI group had significant improvements in diastolic blood pressure, triglycerides, and HDL cholesterol. GLB-TBI attendance was 89.6% and weekly self-monitoring of diet and activity was 68.8%. Relative to baseline, the GLB-TBI compliant group (≥80% attendance; ≥85% self-monitoring; n = 10) had a statistically significant decrease in weight at each assessment, the noncompliant group had a significant decrease between 6 and 12 months (n = 17), with no change in weight in the attention control group (n = 27). Conclusions Findings suggest for adults with TBI who are overweight or obese, participation in the GLB-TBI can significantly reduce weight and metabolic risk factors and increase self-reported habits for diet and exercise. [ABSTRACT FROM AUTHOR]