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Background Lifestyle interventions are first-line therapy for non-alcoholic fatty liver disease (NAFLD). Aims To examine the prevalence of NAFLD among participants of the University of Michigan Metabolic Fitness (MetFit) Programme and to assess the impact of this programme on weight, metabolic and liver-related parameters among patients with and without NAFLD. Methods Adults who completed the programme between 2008 and 2016 were included. Clinical and laboratory data were collected at enrolment, and at 12 and 24 weeks. NAFLD was defined based on liver biopsy, imaging or clinical diagnosis. Results The cohort (N = 403; 253 12-week, 150 24-week) consisted primarily of middle-aged (median 54 years) white (88%) men (63%) with severe obesity (median BMI 37.4). 47.6% met criteria for NAFLD. At baseline, NAFLD patients were younger (52 vs 55 years), had higher weights and more metabolic derangements (higher fasting insulin and triglyceride, lower high-density lipoprotein-cholesterol). At programme completion, 30% achieved weight reduction ≥5%, 62% resolution of hypertriglyceridaemia, 33% resolution of low HDL, 27% resolution of impaired fasting glucose and 43% normalisation of alanine aminotransferase. Endpoints were unaffected by NAFLD. Longer programme duration (OR 6.7, 95% CI 3.6-12.3) and white race (OR 3.83, 95% CI 1.04-1.76) were independent predictors of ≥5% weight loss. Conclusions Nearly half of the patients referred to a structured lifestyle programme for metabolic syndrome had NAFLD. Although baseline metabolic derangements were more pronounced among NAFLD patients, the programme was equally efficacious in achieving weight loss and resolving metabolic syndrome components. Programme duration was the most important predictor of response.