Abstract Study objective The objective of this study is to evaluate health-related quality of life as a risk factor for subsequent emergency department (ED) utilization in a cohort of patients with asthma. Methods We conducted a 1-year prospective cohort study of 1,406 adult asthma patients. Baseline physical and mental health status were measured using the Physical Component Summary and Mental Component Summary scores from the Short Form-12 health status survey. Asthma-specific health-related quality of life was measured with the mini–Asthma Quality of Life Questionnaire. Multivariable regression was used to assess the independent association between baseline Physical Component Summary, Mental Component Summary, and Asthma Quality of Life Questionnaire scores and asthma-related ED visits during the subsequent year. Results During the 1-year follow-up period, 116 patients made at least 1 asthma-related ED visit. After adjustment for multiple sociodemographic and clinical factors, both the Physical Component Summary score (odds ratio [OR] 1.72; 95% confidence interval [CI] 1.46 to 2.02) and the Asthma Quality of Life Questionnaire score (OR 1.34; 95% CI 1.18 to 1.52) were associated with subsequent asthma-related ED utilization. In contrast, overall mental health status was not associated with subsequent asthma-related ED utilization (OR 1.17; 95% CI 0.96 to 1.44). Conclusion Overall physical health status and asthma-specific quality of life predict subsequent ED utilization. Health-related quality of life may be useful in identifying patients at increased risk for asthma exacerbation requiring emergency care.