BACKGROUND: Opioids are widely prescribed for their analgesic properties. Chronic opioid use is a persistent problem in the US. Nevertheless, little is known about its prescribing and utilization patterns and overall expenditures. OBJECTIVE: This study examined secular trends in opioid prescription drug utilization and expenditures, along with factors associated with opioid prescription drug use in US physician offices. METHODS: National Ambulatory Medical Care Survey (NAMCS) and Medical Expenditure Panel Survey (MEPS) data (2006-2010), both nationally representative surveys, were used to assess the trend, predictors of opioid prescription among US adults (more than 18 years) and the opioid-associated expenditures as a whole and borne by the patients in outpatient settings. RESULTS: Opioid prescription drugs use among US adults in outpatient settings, as a percentage of all prescription drugs, showed a gradual increase since 2006, leveling off in 2010. Opioid prescription drug expenditures showed an upward trend from 2009 after declining over three years. Mean out-of-pocket payments per prescription steadily declined over study period. LIMITATIONS: Cross-sectional nature and visit based information of NAMCS do not provide the actual prevalence and the reason for opioid prescription. CONCLUSIONS: Given the upward trend in opioid prescription drug utilization and associated expenditures, clinicians may benefit from evidence-based methods of monitoring prescription opioid use to prevent misuse, abuse, and other adverse patient outcomes. FUNDING: Drs. Qureshi, Haider, Ball, Horner and Bennett's efforts are partially supported by the University of South Carolina's ASPIRE I. Dr. Wooten's effort is funded by the National Institute on Drug Abuse (K01DA037412).