OBJECTIVE: To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk. DESIGN: After screening, patients entered a two-week single-blind placebo lead-in period, during which they followed a mildly hypocaloric diet, before being randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years. SETTING: The study was conducted at 33 primary care centres in Sweden. SUBJECTS: A total of 382 obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186). MAIN OUTCOME MEASURES: Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c. RESULTS: After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P or = 5% (54.2% vs. 40.9%; P