Objectives: Asthma can be associated with substantial productivity loss and activity impairment, particularly among those with the most severe disease. We sought to assess the performance characteristics of an asthma-specific adaptation of the Work Productivity and Activity Impairment Questionnaire (WPAI:Asthma) in patients with either severe or difficult-to-treat asthma., Methods: We analyzed 2529 subjects from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. The WPAI:Asthma was administered at baseline and at 12 months. Asthma control and quality-of-life were simultaneously assessed using the Asthma Therapy Assessment Questionnaire and Mini-Asthma Quality-of-Life Questionnaire, respectively., Results: Severe versus mild-to-moderate asthma was associated with a greater percentage of impairment at work (28% vs. 14%), at school (32% vs. 18%), and in daily activities (41% vs. 21%). At baseline, greater asthma control problems correlated with higher levels of impairment as measured by the WPAI (work: r = 0.54, school: r = 0.37, activity: r = 0.55). Over the 12-month follow-up period, improved quality-of-life correlated with decreased levels of impairment (work: r = -0.42, school: r = -0.36, activity: r = -0.48). In multivariate analyses, greater than 10% overall work impairment at baseline predicted emergency visits (OR 2.6 [1.6, 4.0]) and hospitalization (OR 4.9 [1.8, 13.1]) at 12 months., Conclusions: The WPAI:Asthma correlates with other self-reported asthma outcomes in the expected manner and predicts health-care utilization at 12 months when administered to patients with severe or difficult-to-treat asthma.