Epinephrine can be lifesaving in episodes of anaphylaxis, yet it is underprescribed and underused. Tracking of epinephrine refills over time for patients with a diagnosis of anaphylaxis has not been reported. This study reports on the refill history of 14,677 patients in a large HMO who received an initial dispensing of EpiPen (Dey Pharma, Basking Ridge, NJ) or EpiPen Jr between 2000 and 2006. A total of 6,776 (46%) refilled at least once. Twenty-five percent of the patients who were in the cohort for 5 years or more refilled multiple times, and 11% refilled consistently at all expected refill times. Infants through children 12 years of age were more likely to receive a refill dispensing (63%) compared with teenagers and adults (40%). The most common ICD-9 codes that were linked to the initial epinephrine dispensing were allergic disorder (37%), miscellaneous anaphylaxis/angioedema (23%), hymenoptera/insect bite or sting (14%), and specific or nonspecific food allergy (11%). A total of 79% of patients with a food-related ICD-9 code and 59% of patients with an insect sting-related ICD-9 code refilled epinephrine at least once. An opportunity exists to identify system-based as well as personal barriers in an ongoing effort to provide patients at risk with the tools and empowerment that could reduce their risk during life-threatening anaphylactic reactions.