OBJECTIVE: To compare the feasibility, reliability, validity and sensitivity to change of the Spanish version of the Juniper Quality of Life Questionnaire (AQLQ), Juniper Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and Marks Asthma Quality of Life Questionnaire (Marks-AQLQ) for use in clinical practice. METHODS: Eight hundred seventy-eight patients, with a diagnosis of mild to moderate asthma, were randomly assigned to receive one of the 3 questionnaires. Montelukast was added to the patients with uncontrolled asthma. Feasibility was assessed using mean time of administration and percentage of missing responses. Internal consistency and reliability was assessed using Cronbach's alpha and the intraclass correlation coefficient (ICC). Construct validity was assessed by correlating questionnaire scores with EuroQoL-5D scores and symptoms. Responsiveness was assessed by calculating the standardized effect size (SES). RESULTS: Mean administration time was 7, 8 and 13 minutes for Mini-AQLQ, Marks-AQLQ and AQLQ respectively. On the Mini-AQLQ and Marks-AQLQ 3.3 and 3.8 % patients had missing responses compared with 11.1% on the AQLQ. For Mini-AQLQ, Marks-AQLQ and AQLQ Cronbach's alpha were 0.85, 0.90 and 0.91 respectively and ICC were 0.63, 0.74 and 0.78. In univariate analyses, significant differences in the three questionnaires scores were observed according to gender, disease severity, symptoms and use of on-demand short acting beta-agonists. The cross-sectional and longitudinal correlations were strong between the questionnaires and EQ-5D as well as between the questionnaires and symptoms. The Pearson correlation between the questionnaires and FEV1 (% of predicted value) was weak. The effect size between both visits were 0.91, 0.7 and 1 for Mini-AQLQ, Marks-AQLQ and AQLQ respectively. CONCLUSIONS: The three questionnaires are reliable, valid and sensitive to changes. Mini-AQLQ is better on feasibility making it a more efficient way to assess quality of life in adults with mild to moderate asthma.