Although cognitive impairment has been shown to adversely affect antiviral medication adherence, a subset of cognitively impaired adults nonetheless are able to adequately adhere to their medication regimen. However, little is known about factors that serve as buffers against suboptimal adherence among the cognitively impaired. This study consisted of 160 HIV-positive, cognitively impaired adults (Global Deficit Score ≥ 0. 50) whose medication adherence was monitored over 6-months using an electronic monitoring device (MEMS caps). Logistic regressions were run to determine psychosocial variables associated with medication adherence. Higher self-efficacy and treatment related support, a stable medication regimen, stable stress levels, and absence of current stimulant use were predictive of optimal adherence. A distinct array of psychosocial factors was found that buffer against the adverse effects of cognitive impairment on medication adherence. Assessment and interventions targeting these factors may improve adherence rates among cognitively impaired adults.