Obesity is a chronic disease with a marked impact on health and the prevalence of obesity in Croatia is rapidly rising. Since obesity plays a significant role in the etiology of cardiovascular diseases, diabetes mellitus type 2 and of some cancers, it is an obvious target of public health activities. Weight-reducing drugs, like sibutramine, in combination with diet, exercise and behavioral changes have a role in the management of obesity. Sibutramine acts centrally as a serotonergic and noradrenergic reuptake inhibitor. It reduces body weight by enhancing satiety and stimulating thermogenesis. The aim of this multicenter prospective study was to evaluate the efficacy, tolerability and safety profile of sibutramine in the treatment of overweight patients in Croatia. Patients received 10 mg of sibutramine daily for 12 weeks. The main outcome measures were changes in body weight, BMI, waist and hip circumferences, laboratory assessments (serum triglicerida, cholesterol, glucose, HbA1c), blood pressure and heart rate profile. Of 461 patients included (mean BMI = 35.81+/-6.48 kg/m2, mean age = 43.65+/-10.90 years), 392 completed the study. Three months of sibutramine treatment lead to a significant reduction in body weight, BMI, waist and hip circumferences and improvement in metabolic parameters. Loss of over 5% of their initial body weight was found in 359 patients (91.58%), while 179 patients (45.66%) achieved weight loss over 10%. A decrease of both systolic (-3.39%) and diastolic (-3.75%) blood pressure was noted, while the pulse rate rose slightly (+0.13%). Adverse events were reported by 124 (26.90%) patients, but they precipitated only 17 (3.69%) withdrawals. Results of our study confirmed that sibutramine is an effective and safe weight-reducing drug.