OBJECTIVES: Previous research has indicated a strong relationship between asthma symptoms and asthma-specific quality of life (QoL).  However, past measures of asthma-specific QoL typically confound symptoms and functional impairment with QoL, which in turn may cause a misleadingly high inter-correlation.  The current research uses a newly developed measure of asthma-specific QoL (the RAND-Impact of Asthma on Quality of Life; RAND-IAQL) that controls for asthma symptoms and functional impairment while assessing the degree of asthma impact or burden.  Using this new measure, we model the relationship between asthma specific quality of life, generic quality of life, asthma control, and comorbid conditions commonly associated with asthma. METHODS: Using a diverse sample of adults with asthma (N­=2032), we use structural equation models (SEM) to establish the relationships and suppression effects of asthma control, symptoms, comorbidities (e.g., COPD, Sinusitis), and multiple PROMIS QoL instruments (including anxiety and social QoL) on the prediction of asthma-specific QoL.  SEM models will be presented sequentially in order to evaluate the relative utility of increasingly complex models using likelihood ratio tests and changes in the amount of IAQL variance that is accounted for by each added predictor (latent) variable. RESULTS: Close fitting SEM models suggest that “interference” caused by asthma, an indicator commonly used to measure asthma control, is most strongly related to asthma-specific QoL.  Contrary to the research literature, symptoms of asthma (including shortness of breath, wheezing, and cough) and comorbid diseases are less strongly related to asthma specific QoL than are general assessments of interference and generic measures of anxiety and limitations in social functioning. CONCLUSIONS: Asthma-specific QoL is best understood as the degree to which asthma impacts or burdens ones daily life.  While asthma symptoms, control, and general QoL are highly inter-correlated, asthma control (primarily interference) is differentially predictive of asthma-specific QoL.