Little is known about the relationship between pain and aberrant use of prescription analgesics in persons living with HIV. We examined the predictive and concurrent associations among pain, aberrant use of opioids, and problem drug use history in a nationally representative longitudinal sample of 2267 HIV+ persons. Covariance structure analyses tested a conceptual model wherein HIV + patients with a history of problematic drug use (n = 870), compared to those without such history (n = 1397), were hypothesized to report more pain and aberrant opioid use, as well as use of opioids specifically for pain at baseline and 6 and 12 month follow-ups, after controlling for key sociodemographic characteristics. In support of the hypothesized model, patients with a history of problematic drug use reported more pain, and were more likely to report aberrant use of prescription analgesics, as well as use of such medications specifically for pain, compared to patients without such history. We also found a trend toward greater stability of aberrant opioid use over time in problem drug users compared with non-problem users suggesting a persistent pattern of inappropriate medication use in the former group. Our findings suggest that even though HIV+ persons with a history of problematic drug use report on-going patterns of using prescription analgesics specifically for pain, these patients continued to experience persistently higher levels of pain, relative to nonproblem users. Among non-problem users, pain was not linked to aberrant use of opioids, but was linked to the use of such medications specifically for pain.