Weight loss drugs have been developed to reduce the comorbidities associated with excess weight. We conducted a meta-analysis of the efficacy of orlistat and sibutramine on weight, body mass index, waist circumference and cardiovascular risk factors in overweight adolescents. MEDLINE and the Cochrane Library were searched for relevant articles using MESH terms and keywords. Studies were included if they had reported quantitative estimates and standard deviations of the association between each weight loss drug and weight, with information on at least one cardiovascular risk factor. A total of eight trials (three orlistat and five sibutramine) with information on 1391 individuals was included in the present analysis. The mean decrease in weight between the intervention and control groups was 5.25 kg (95% confidence interval: 3.03-7.48) after a minimum follow-up of 6 months. There was evidence of statistical heterogeneity between the studies (I2 = 76%) that was no longer apparent after exclusion of trials of orlistat (mean weight decrease = 5.32 kg; I2 = 38%). There was little evidence that treatment was associated with adverse effects on cardiovascular risk factors but this requires verification from future large trials with longer study follow-up.