BACKGROUND: Cooccurring pain, mood disorders, and substance abuse are common in HIV-infected patients. Our objective was to investigate the relationship between pain, alone and in the context of mood disorders and substance abuse, on clinic utilization, antiretroviral therapy adherence, and virologic suppression. METHODS: Pain, mood disorders, and substance abuse were assessed at the first visit. No-show and urgent visits were measured over a 1-year period. Models were adjusted for age, race, sex, insurance status, CD4(+) T-lymphocyte count, and HIV risk factor. RESULTS: Among 1521 participants, 509 (34%) reported pain, 239 (16%) had pain alone, 189 (13%) had pain and a mood disorder, and 30 (2%) had pain and substance abuse. In univariate models, participants with pain, mood disorders, and substance abuse had higher odds of a no-show visit than those without these conditions [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-1.8; OR, 1.5; 95% CI, 1.2-1.9; OR, 2.0; 95% CI, 1.4-2.8, respectively]. In the multivariable model, pain increased the odds of a no-show visit only in participants without substance abuse (OR, 1.5; 95% CI, 1.1-1.9) and pain reduced the odds of a no-show visit in participants with substance abuse (OR, 0.5; 95% CI, 0.2-0.9; P for interaction = 0.0022). CONCLUSIONS: In this study, pain increased the odds of no-show visits but only for participants without substance abuse. Because pain, mood disorders, and substance abuse are highly prevalent in HIV-infected patients, our findings have implications for HIV treatment success. Interventions that incorporate pain management may be important for improving health outcomes in patients living with HIV infection.