Ethnic minorities in the West exhibit a higher prevalence of obesity and also under-achieve in weight management compared to White Caucasians. A systematic review of randomized controlled trials (RCTs) in adults (mean age ≥18 years, duration ≥6 months and published in the English language) was undertaken to evaluate the effectiveness of antiobesity drugs in ethnic minorities and White Caucasians. Data sources between 1990 and 2010 were searched including MEDLINE, EMBASE, Cochrane Controlled Trials Register, CINAHL and references cited in the included studies of other reviews. Eighteen RCTs that met the inclusion criteria were included in this review (6 sibutramine and 12 orlistat). A random effects model was used for meta-analysis. An indirect comparison of weight loss in sibutramine-treated patients in ethnic minorities was significantly lower than in White Caucasians: −2.7 kg (95% CI: −3.1 to −2.3) versus −4.4 kg (95% CI: −5.0 to −3.8), respectively. For orlistat, weight loss was similar in the two groups: −2.3 kg (95% CI: −2.6 to −2.0) in ethnic minorities and −2.8 kg (95% CI: −5.1 to −0.5) in White Caucasian participants. Overall, there were few studies of weight loss pharmacotherapy for comparison of this review and it was not possible to analyse data based on ethnic groupings. More ethnically tailored studies are needed to assess the most effective weight loss strategies in these most metabolically vulnerable groups.