Background: Asthma patients experience impairments in health-related quality of life (HRQL). Interventions are available to improve HRQL. EQ-5D-5L is a common generic tool used to evaluate health interventions. However, there is debate over whether the use of this measure is adequate in asthma patients.Methods: We used data from 371 asthma patients participating in a pulmonary rehabilitation (PR) program from the EPRA randomized controlled trial. We used four time points: T0 randomization, T1 start PR, T2 end PR, T3 3 months follow-up. We calculated floor and ceiling effects, intra-class correlation (ICC), Cohen's d, and regression analysis to measure the sensitivity to changes of EQ-5D-5 L (EQ-5D index and Visual Analog Scale (VAS)) and the disease-specific Asthma Quality of Life Questionnaire (AQLQ). Furthermore, we estimated the minimally important difference (MID). Based on the Asthma Control Test (ACT) scores, we defined three groups: 1. ACT-A (ACT> 19) controlled asthma, 2. ACT-B (14 < ACT <= 19) not well-controlled asthma, and 3. ACT-C (ACT <= 14) very poorly controlled asthma.Results: Only the EQ-5D index showed ceiling effects at T2 and T3 (32%). ICC (between T0 and T1) was moderate or good for all measures. Cohen's d at T2 and T3 was better at differentiating between ACT-A and ACT-B than between ACT-B and ACT-C. The EQ-5D index showed moderate effect sizes (0.63-0.75), while AQLQ showed large effect sizes (0.74-1,48). VAS was responsive to pronounced positive and negative ACT changes in every period, and AQLQ mostly to the positive changes, whereas the EQ-5D index was less responsive. We estimated a MID of 0.08 for the EQ-5D index, 12.3 for VAS, and 0.65 for AQLQ.Conclusion: All presented HRQL tools had good discriminatory power and good reliability. However, EQ-5D-5 L did not react very sensitively to small changes in asthma control. Therefore, we would suggest using supplementary measures in addition to EQ-5D-5 L to evaluate asthma-specific interventions more comprehensively.