Although highly active antiretroviral therapy (HAART) is an effective treatment for HIV, many physicians withhold this treatment from HIV-positive injecting drug users (IDUs) because of fears of non-adherence and consequent development of antiretroviral resistance. Little is known, however, about whether the rates of resistance differ between IDUs and non-IDUs. We did a meta-analysis of studies that compared antiretroviral resistance rates in IDUs (current or previous) with those in HIV-positive patients infected by other routes and who had never injected drugs. We used a random-effects model to investigate overall resistance rates and resistance to individual drug classes. Of 181 potential studies, 27 were eligible for review. We were able to extract data from 14 studies, but two were excluded because of a very small sample size of IDUs or data being available only from a secondary analysis. Thus we included 12 studies in the meta-analysis, involving 9055 patients, of which 2054 (23%) were IDUs. The risk of development of antiretroviral resistance did not differ significantly between IDU and non-IDU (odds ratio 1.04, 95% CI 0.74-1.45, p=0.84). Rates of loss to follow-up and virological failure were similar in IDU and non-IDU samples. Existing evidence does not support the common practice of withholding antiretroviral therapy from HIV-positive IDU on the basis of an elevated risk of antiretroviral resistance. Therapeutic guidelines should consider reassessment of this issue.