This study determined the associations between opioid abuse, dependence, and poisonings on costs and comorbidities in the Medicaid population. Medicaid patients in the Medicaid Analytic eXtract (MAX) files from 2002 to 2003 with 12 months of continuous eligibility, age >or=12 years, and with an opioid abuse/dependence-related diagnosis, including opioid abuse, dependence, or poisoning, in 2002 (index date) were matched 3:1 to Medicaid patients with no such diagnosis (controls). Medical costs by claim type incurred 12 months post index date were compared as was the prevalence of select comorbidities. The authors conducted a two-step multivariate regression analysis adjusted for patient characteristics that could influence cost outcomes. Opioid abuse/dependence prevalence was 8.7 per 1000 in 2002-2003. A total of 50,162 patients with abuse or dependence-related diagnoses were matched to 150,486 control patients. Total costs were significantly higher for the abuse/dependence patients ($14,537) than matched controls ($8,663) (P < .001). When controlling for baseline characteristics, adjusted costs continued to be higher for abuse/dependence patients ($23,556 versus $8,436; P < .001). A total of 83.7% of abuse/dependence patients and 51.6% of controls had >or=1 of the predefined comorbidities. Other substance abuse (odds ratio [OR] 9.4), hepatitis A, B, or C (OR 8.8), and poisonings (OR 8.5) were highly associated with a diagnoses for opioid abuse or dependence (P < .001). Medicaid opioid abuse/dependence patients had more comorbidities and higher medical costs in 2002-2003 than Medicaid control patients. Successful interventions to prevent opioid abuse and manage comorbidities could help to reduce costs associated with opioid abuse in the Medicaid population.