Background The prescribing pattern of epinephrine over time is an indicator of the secular trend of anaphylaxis. However, it is not well known in a population level in the United States. Objective To evaluate the trend of prescriptions for epinephrine autoinjectors in Olmsted County, Minn, residents. Methods Outpatient prescriptions for epinephrine were identified among residents of Olmsted County, Minn, between January 1, 2004, and December 31, 2010. We used the first prescription per patient per year, and the first prescription per patient during the study period to calculate incidence rates. Incidence rates per 100,000 person-years were calculated using patients prescribed epinephrine per year as the numerator and age- and sex-specific counts of the population of Olmsted County as the denominator. The relationships of age group, sex, and year of prescription with incidence rates were assessed by fitting Poisson regression models using the SAS procedure GENMOD. Results The overall incidence rate of epinephrine autoinjector prescriptions during the study period was 757 per 100,000 person-years (95% confidence interval: 740-774). The prescription rates per patient per year increased over time, with an annual rate of increase of 8% (P < .001), but the rates per patient remained stable (P = .077). For each year, incidence rates overall were higher in women compared with men (P < .001). From ages 0 to 19, incidence rates were higher in boys compared with girls. At age 20 and above, incidence rates were higher in women compared with men. Conclusions The overall rate of epinephrine autoinjector prescriptions increased, but the rate of first-time prescriptions was stable from 2005 to 2010. In childhood, boys were more likely to receive a prescription than girls, but this reversed in later ages.