Objective: To study whether major weight loss causes sustained improvement in blood lipids and haemostatic profile in obese subjects, and to compare the influence of two different slimming and maintenance regimens. Design: Two-stranded randomized intervention study. Setting: University Department. Subjects: Thirty-six out of 43 obese patients recruited from out-patient waiting list completed the study. Interventions: Weight loss was achieved by very low energy formula diet (2 MJ/d for 8 weeks, n = 18), or low-energy conventional diet (5 MJ/d for 17 weeks, n = 18), both combined with anorectic compound. Participants were re-randomized to consume low far diet ad libitum (n = 16), or energy-restricted diet (n = 20) for weight maintenance during 24 weeks. Main outcome measures: Plasma lipids, fibrinogen, factor VII coagulant activity (FVIIc), and plasminogen activator inhibitor type 1 (PAI-1) antigen. Results: Weight loss averaged 13.6 kg (95% CI: 12.3-14.9 kg). After 24 weeks' weight maintenance, plasma total cholesterol was 9% lower, high density lipoprotein cholesterol 5% higher, triglycerides 30% lower, FVIIc 12% lower, fibrinogen 6% lower, and PAI-1 antigen 34% lower than at baseline (all changes highly significant). There were no significant differences between slimming or maintenance regimens. Conclusions: Major weight loss is associated with sustained and marked improvements in blood lipids and hemostatic profile, irrespective of the tested slimming and maintenance regimens. Sponsorship: 2 Nycomed DAK A/S, Roskilde, Denmark, and the Danish Medical Research Council.