The present study assesses the impact of methamphetamine (METH) on antiretroviral therapy (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors [i.e., major depressive disorder (MDD), antisocial personality disorder (ASPD), and attention deficit disorder (ADHD)] for ART non-adherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+ /METH+ ; n=67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+ /METH - ; n=50). Ancillary analyses compared these groups with a small group of HIV+ /METH+ persons with current METH abuse/dependence (HIV+ /CU METH+ ; n=8). Non-adherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH- participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART non-adherence (p's < 0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART non-adherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of non-adherence) than lifetime METH+ users and HIV+ /METH- participants and that neurocognitive impairment was associated with non-adherence (p's < 0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication non-adherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking.