Abstract  Objective: The specific objectives of this study were to: 1) study the effect of moderate-to-severe asthma on patient's Health-Related Quality of Life (HRQoL) as measured by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and 2) evaluate the construct validity of a modified and shortened version of the Living With Asthma Questionnaire (ms-LWAQ) using the SF-36 as a concomitant measure of HRQoL. Methods: Cross-sectional, telephone or mail surveys of asthmatic patients enrolled in two central Florida managed care organizations. Results: All subscales of the SF-36 and four subscales of the ms-LWAQ demonstrated adequate reliability in this population (Cronbach >0.72). The subscales of the SF-36 most affected by patient's asthma were: general health perceptions, vitality and physical role functioning. These three subscales were correlated with four subscales of the ms-LWAQ: consequences, seriousness, affect and leisure. Six of the eight SF-36 subscales and all of the ms-LWAQ subscales were associated with patient's emergency department and hospital utilization. Conclusion: The ms-LWAQ and SF-36 are valid as useful measures of asthma patient's HRQoL in this cross-sectional study. Severity of disease, as measured by health care utilization, was significantly associated with HRQoL.