ABSTRACT: OBJECTIVE:To determine the effectiveness of a novel interdisciplinary treatment compared with usual care on weight loss in overweight and obese adult volunteers. DESIGN:Single blinded controlled trial. Participants randomly assigned to usual care (C, general guideline-based diet and exercise advice), intervention (I, interdisciplinary protocol) or intervention + a healthy food supplement (30 g walnuts/day) (IW). SETTING:Community based study, Illawarra region, south of Sydney, Australia. PARTICIPANTS:Generally well volunteer adult residents, 25-54 years, body mass index (BMI) 25-40kg/m2 were eligible. At baseline 439 were assessed, 377 were randomised, 298 completed the 3-month intensive phase and 178 completed the 12-month follow-up. INTERVENTIONS:Treatment was provided at clinic visits intensively (0 months, 1 month, 2 months, 3 months) then quarterly to 12 months. Support phone calls were quarterly. All participants underwent blinded assessments for diet, exercise and psychological status. PRIMARY AND SECONDARY MEASURES:The primary outcome was difference in weight loss between baseline and 12 months (clinically relevant target 5% loss). Secondary outcomes were changes in blood pressure, fasting blood glucose and lipids, and changes in diet, exercise and psychological parameters. RESULTS:At 12 months, differences in weight loss were identified (p<0.001). The I group lost more than controls at 3 months (91.11 (92.23,90.00), p<0.05) and the IW more than controls at 3 months (91.25 (92.35,90.15), p<0.05) and 6 months (92.20 (93.90,90.49), p<0.01). The proportion achieving 5% weight loss was significantly different at 3 months, 6 months and 9 months (p=0.04, p=0.03, p=0.03), due to fewer controls on target at 3 months, 6 months and 9 months and more IW participants at 6 months. Reductions in secondary outcomes (systolic blood pressure, blood glucose/lipid parameters and lifestyle measures) followed the pattern of weight loss. CONCLUSIONS:An interdisciplinary intervention produced greater and more clinically significant and sustained weight loss compared with usual care. The intensive phase was sufficient to reach clinically relevant targets, but long-term management plans may be required. TRIAL REGISTRATION NUMBER:ANZCTRN 12614000581662; Post-results.