Background: The recent Global Initiative for Asthma management strategy recommends achieving symptom control and minimizing the future risk of poor outcomes as priorities for asthma management. Objective: The objective was to quantify the association between symptom control and health-related quality of life in asthma. Methods: In a prospectively recruited random sample of adults with asthma, we ascertained symptom control and measured health-related quality of life using a generic (EuroQol five-dimensional questionnaire [EQ-5D]) and a disease-specific (Asthma Quality of Life Questionnaire) instrument, to estimate EQ-5D and five-dimensional Asthma Quality of Life Questionnaire (AQL-5D) utilities, respectively. We measured the adjusted difference in utilities across symptom control levels and calculated the loss of predictive efficiency due to aggregating multiple symptoms into one symptom control variable. Results: The final sample included 958 observations from 494 individuals (mean age at baseline 52.2 ± 14.5 years; 67.0% women). Asthma was symptomatically controlled, partially controlled, and uncontrolled in 269 (28.1%), 367 (38.3%), and 322 (33.6%) observations, respectively. A person with symptomatically uncontrolled asthma would gain 0.0512 (95% CI 0.0339-0.0686) in EQ-5D or 0.0802 (95% CI 0.0693-0.0910) in AQL-5D utilities by achieving symptom control. The loss of predictive efficiency was 55.4% and 27.6% for EQ-5D and AQL-5D utilities, respectively. Conclusions: Asthma symptom control status corresponds well with both generic and disease-specific quality-of-life measures. The trade-off, however, between ease of use and predictive power should be reconsidered in developing simplified measures of control. Our results have direct relevance in informing decision-analytic models of asthma and deducing the effect of interventions on quality of life through their impact on asthma control. © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR).