OBJECTIVES: Evaluation of the cost of delivering IV opioids in the emergency department (ED) for the treatment of acute pain has been limited to date.  This study estimates the cost of delivering an initial dose of an IV opioid to ED patients. METHODS: Descriptive analyses using the Premier database (2013-2014) of > 600 US hospital EDs were conducted on the cost of starting an IV and delivering an initial dose of an IV opioid in EDs.  Average costs of each component were aggregated for total costs.  Direct acquisition and indirect cost (labor, pharmacy, etc.) were included. RESULTS: Over 24 months, 7,327,299 patients received IV opioids in 614 EDs in the US (approximately one-tenth of EDs in the US).  Of these patients, 58% were not admitted to the hospital.  Morphine (56%), hydromorphone (45%) and fentanyl (25%) were the most frequently administered IV opioids.  Average [median; interquartile range] costs include initiating an IV ($62 [$62; $60-66]), IV catheter ($4 [$3; $2-3]), infusion pump tubing ($15 [$18; $8-21]), infusion pump to maintain IV patency ($37 [$26; $23-64]), 250 mL saline bag ($15 [$13; $9-19]), 2% lidocaine for local anesthesia for line placement ($5 [$4; $3-6]) and the cost of a single dose of morphine 5 mg ($6 [$4; $2-7]), hydromorphone 1 mg ($7 [$5; $3-9]) or fentanyl 100 mcg ($7 [$6; $4-10]).  Aggregated mean IV opioid total costs per patient for a single standard dose of opioid were $143 (morphine), $144 (hydromorphone) and $145 (fentanyl).   CONCLUSIONS: The cost of setting up an IV line to administer an opioid is substantial. Since the majority of patients receiving IV opioids are discharged from the ED, the ultimate use for this IV line is limited.  The development of a rapid-acting, non-invasive analgesic for ED use could be advantageous from both a cost and patient-benefit standpoint.