BACKGROUND Emergency Medical Services (EMS) preparedness and availability of essential medications are important to reduce morbidity and mortality from mass-casualty incidents (MCIs). OBJECTIVES This study describes prehospital medication administration during MCIs by different EMS service levels. METHODS The US National EMS Public-Release Research Dataset maintained by the National Emergency Medical Services Information System (NEMSIS) was used to carry out the study. Emergency Medical Services activations coded as MCI at dispatch, or by EMS personnel, were included. The Center for Medicare and Medicaid Services (CMS) service level was used for the level of service provided. A descriptive analysis of medication administration by EMS service level was carried out. RESULTS Among the 19,831,189 EMS activations, 53,334 activations had an MCI code, of which 26,110 activations were included. There were 8,179 (31.3%) Advanced Life Support (ALS), 5,811 (22.3%) Basic Life Support (BLS), 399 (1.5%) Air Medical Transport (AMT; fixed or rotary), and 38 (0.2%) Specialty Care Transport (SCT) activations. More than 80 different medications from 18 groups were reported. Seven thousand twenty-one activations (26.9%) had at least one medication administered. Oxygen was most common (16.3%), followed by crystalloids (6.9%), unknown (5.2%), analgesics (3.2%) mainly narcotics, antiemetics (1.5%), cardiac/vasopressors/inotropes (0.9%), bronchodilators (0.9%), sedatives (0.8%), and vasodilators/antihypertensives (0.7%). Overall, medication administration rates and frequencies of medications groups significantly varied between EMS service levels (P<.01) except for "Analgesia (other)" (P=.40) and "Pain medications (nonsteroidal anti-inflammatory drug; NSAID)" (P=.07). CONCLUSION Medications are administered frequently in MCIs, mainly Oxygen, crystalloids, and narcotic pain medications. Emergency Medical Services systems can use the findings of this study to better prepare their stockpiles for MCIs.