To examine the prevalence of pain, substance use disorder (SUD) diagnoses, and opioid analgesic prescription patterns among veterans infected with the hepatitis C virus (HCV), a retrospective review of the medical records of 8,224 HCV-positive (HCV+) veterans was performed. Twenty-nine percent and 46% of HCV+ patients were prescribed opioids in the prior one and three years, respectively. Sixty-seven percent of HCV+ patients had documented pain diagnoses and 56% had SUD diagnoses. Patients with co-occurring pain and SUD were less likely to be prescribed opioids than patients with pain only (prior year: 36% vs. 43%, P<0.001; three years: 56% vs. 60%, P<0.01). There were no differences in numbers of early opioid prescription fills or numbers of opioid prescribers when comparing patients with co-occurring pain and SUD to patients with pain only. Veterans with co-occurring pain and opioid use disorder had fewer early opioid fills than veterans with pain only (prior year: 2.6 vs. 5.3 days, P<0.01; three years: 6.1 vs. 13.4 days, P<0.001). These data demonstrate that pain and SUD diagnoses were common among HCV+ patients, and that opioids were frequently prescribed. Co-occurring SUD was not associated with indicators of prescription opioid misuse.