There is a great deal of concern about opioid use in veterans, particularly those who served in Afghanistan (OEF) and Iraq (OIF and OND). The current study provides a detailed pharmacoepidemiologic analysis of opioid use among OEF/OIF/OND veterans from FY09 to FY12. Data from 3 data repositories from the Veterans Health Administration (VHA) were used to describe demographic, clinical, and medication characteristics associated with opioid use among OEF/OIF/OND veterans and among those with TBI. Logistic regression models were used to identify risks associated with chronic opioid use in FY12. Approximately 23% of all OEF/OIF/OND veterans and 35% of those with TBI received any opioid medications. Most received moderate doses ranging from 26 to 30 mg morphine equivalent dose daily. Median days of opioid use for all OEF/OIF/OND veterans were 30 to 40 days. Factors associated with chronic use in both groups included young age, male sex, white race, being married, and living in rural areas. A diagnosis of PTSD (odds ratio [OR] = 1.22, P < 0.0001), major depressive disorder (OR = 1.14, P < 0.0001), and tobacco use disorder (OR = 1.18, P < 0.0001) were strongly associated with chronic opioid use. Back pain was also strongly associated with chronic use (OR = 2.50, P < 0.0001). As pain severity increased the odds of chronic opioid use also increased: mild pain (OR = 3.76, P < 0.0001), moderate pain (OR = 6.80, P < 0.0001), and severe pain (OR = 8.49, P < 0.0001). Opioid use among OEF/OIF/OND veterans is characterized by moderate doses that are used over relatively long periods of time by a minority of veterans.