ABSTRACT: Background:Asthma is a chronic inflammatory lung disease that affects 18.7 million U.S. adults. Electronic health records (EHRs) are a unique source of information that can be leveraged to understand factors associated with asthma in real-life populations. In this study, we identify demographic factors and comorbidities associated with asthma exacerbations among adults according to EHR-derived data and compare these findings to those of epidemiological studies. Methods:We obtained University of Pennsylvania Hospital System EHR-derived data for asthma encounters occurring between 2011 and 2014. Regression analyses were performed to model asthma exacerbation frequency as explained by age, sex, race/ethnicity, health insurance type, smoking status, body mass index (BMI) and various comorbidities. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2012 to compare findings with those from the EHR-derived data. Results:Based on data from 9068 adult patients with asthma, 33.37% had at least one exacerbation over the four-year study period. In a proportional odds logistic regression predicting number of exacerbations during the study period (levels: 0, 1-2, 3-4, 5+ exacerbations), after controlling for age, race/ethnicity, sex, health insurance type, and smoking status, the highest odds ratios (ORs) of significantly associated factors were: chronic bronchitis (2.70), sinusitis (1.50), emphysema (1.39), fluid and electrolyte disorders (1.35), class 3 obesity (1.32), and diabetes (1.28). An analysis of NHANES data showed associations for class 3 obesity, anemia and chronic bronchitis with exacerbation frequency in an adjusted model controlling for age, race/ethnicity, sex, financial class and smoking status. Conclusions:EHR-derived data is helpful to understand exacerbations in real-life asthma patients, facilitating design of detailed studies and interventions tailored for specific populations.