To investigate the efficacy and tolerability of orlistat in obese adolescents, a prospective, open-label, randomised, controlled pilot trial was performed. A total of 22 adolescents with exogeneous obesity were started on orlistat (120 mg tid) and a daily multivitamin preparation in addition to conventional treatment which included nutritional and lifestyle modification programmes. The control group consisted of 20 obese adolescents who had similar duration of follow-up under conventional treatment alone. Of the 22 patients, 7 dropped out within the 1st month of the trial due to side-effects attributable to orlistat. The remaining 15 patients on orlistat were followed for 5–15 months (average duration of treatment 11.7±3.7 months). The control group was similar in age, sex, and duration of follow-up (10.2±3.7 months, range 6–17 months) to the orlistat group. Compared to initial body weight, patients in the orlistat group lost –6.27±5.4 kg, whereas those in the control group gained 4.16±6.45 kg (P<0.001) during the study period. Patients in the orlistat group lost –7.65%±6.5% of their initial body weight, whereas, those of the control group gained 5.7%±8.3% (P<0.001). The body mass index decreased in the orlistat group by –4.09±2.9 kg/m² while it increased by +0.11±2.49 kg/m² in the control group (P<0.001). Mild gastrointestinal complaints (frequent stools) were experienced by all patients in the orlistat group. Conclusion:Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents; however, gastrointestinal side-effects limit its usefulness in almost one in three adolescents.