Objectives. – To compare changes in anthropometric measures [body mass index (BMI), body weight] of obese patients treated with diet and exercise alone or additionally sibutramine, orlistat or the combination of both drugs, respectively. To describe encountered adverse effects. Methods. – Short-term (12 weeks), randomized, open-labeled trial. A total of 86 patients (18.6% male, age 41.1 ± 8.7 years, BMI: 36.11 ± 4.34 kg/m 2) were randomized to (1) sibutramine group (10 mg/d, n = 22), or (2) orlistat group (3 × 120 mg/d, n = 25), or (3) combination group (10 mg sibutramine/d + 3 × 120 mg orlistat/d, n = 20), or (4) diet group ( n = 19). The primary outcome parameter was a decrease in BMI. Additionally patient-reported adverse effects were reported. Results. – The four interventional groups displayed decreases in BMI as follows: (1) –4.41 ± 1.26 kg/m 2; (2) –3.64 ± 0.97 kg/m 2; (3) –5.12 ± 1.44 kg/m 2 and (4) –2.52 ± 1.36 kg/m 2; with the diet group showing the significantly lowest decrease in BMI compared to the orlistat ( P = 0.004), sibutramine ( P < 0.001) or the combination groups ( P < 0.001), respectively. Decreases in BMI did not statistically differed between the sibutramine group and the combination therapy group ( P = 0.072). However, both treatment groups were significantly more efficient in decreasing BMI than the orlistat group ( P < 0.001). In addition to well-known side effects, such as gastrointestinal disturbances, headache and dry mouth, newly described adverse effects were self-reported hypermenorrhea (13.6%, n = 3) with sibutramine and forgetfulness with orlistat (24%, n = 6). Conclusion. – In our study pharmacotherapy showed significant better results in the short-term management of obesity than dietary regimens alone. Sibutramine and sibutramine in combination with orlistat seemed to be equally effective in terms of weight reduction compared to orlistat monotherapy. Attention should be paid to the possibility of adverse effects.