Cognitive deficits are associated with nonadherence to HIV medications. HIV-positive injecting drug users (IDUs) are at particular risk for nonadherence and cognitive barriers to adherence specific to this population should therefore be identified. The present study assessed the relation of three domains of cognitive functioning, executive functions, memory, and psychomotor speed, to self-reported antiretroviral adherence in a sample of HIV-positive IDUs. Depression, use of alcohol, heroin, cocaine/crack, or marijuana in the last week were also included in the models. Logistic regression analyses showed that only psychomotor slowing was significantly associated with nonadherence. Executive functions, memory, depression, and active alcohol and substance use were unrelated to adherence. No other studies to date have exclusively linked psychomotor slowing to nonadherence in HIV infection. Psychomotor slowing among our study sample was severe and suggests that when evident, such slowing may be a valuable determinant for antiretroviral adherence among IDUs.