OBJECTIVES: Compare health care resource utilization (HCRU) and costs between patients prescribed opioids versus those who were not during emergency department (ED) or inpatient visits. METHODS: Patients with ED/inpatient visits were selected from the MarketScan Commercial and Medicare Supplemental Database linked with the Marketscan Hospital Discharge Database (1/12007–9/30/2009). Patients prescribed opioids in the ED/inpatient setting were assigned to the ‘Opioid Patient (RxOP)’ cohort. The first prescription date was the index date. Among patients not prescribed opioids, the ‘Non-Opioid Patient (NoRxOP)’ cohort, a random date between the first ED/inpatient admission and 30SEPT2009 served as the index date. Additional inclusion criteria were: age older than 12 years at index date, and 12 months of continuous enrollment before and after the index date. Patients with opioid prescriptions during the pre-index period were excluded. Differences in patients’ age, gender, geographic region, comorbidities, and HCRU during the pre-index period were adjusted by 1:1 propensity score (PS) matching (PSM). RESULTS: Overall, opioids were prescribed in 56% of patients in ED, and 71% in inpatient setting. After excluding patients with pre-index opioid use (N=163), among 27,599 eligible patients, 68% (RxOP: N=18,819) were prescribed opioids, and 32% (NoRxOP: N=8,780) were not. The majority of patients (96%, N=18,031) were prescribed immediate-release opioids and 4% (N=788) extended-release opioids (LAO use slightly higher in ED versus inpatient, 6.5% versus 3.7%, p<0.01). Among the 5099 PS matched patients, adjusted results showed that RxOP patients had more inpatient (1.58 vs. 0.36, p<0.01), physician (10.17 vs.8.96, p<0.01) and ED visits (1.12 vs. 0.67, p<0.01) than NoRxOP patients in the follow-up period. RxOP users had twice the total healthcare costs ($49,766 vs. $19,875, p<0.01) than NoRxOp patients.  CONCLUSIONS: A large percentage of patients are prescribed opioids for the first time during ED/inpatient visits and incur a significantly higher resource use and economic burden than those who are not.