The quality of life for respiratory illness questionnaire (QoLRIQ) is an outcome measure for patients with asthma or chronic obstructive pulmonary disease (COPD). This study assessed the longitudinal validity, reliability of the change score and the interpretation of changes on the QoLRIQ in inpatient pulmonary rehabilitation, completed by 108 patients with moderate to severe asthma (39) or COPD (69). Domains and total score of the QoLRIQ changed significant (all p < 0.0002) with standardized response means from 0.46 to 0.90. All QoLRIQ-change scores were significantly correlated with self-rated change in health and in disease symptoms and with change in self-assessed health status (r from 0.2 to 0.61). There were several significant correlations between QoLRIQ-change scores and change in experienced invalidity, emotional well-being, anxiety, depressive symptoms and Rand-36-domains (r from 0.2 to 0.68). The intraclass correlation coefficient of change was 0.90. The size of a minimal important difference (MID), computed from a retrospective global rating of change by the patients and with the standard error of measurement, was 0.5 points on a 7-point response scale. Computation of the MID from retrospective assessment of change may not be valid because this change was significantly correlated to post-treatment health status and significantly higher than serial assessment of change. We conclude that the QoLRIQ is sensitive to change, longitudinally valid and reliable, with a MID of 0.5 points. These results enable the use of the QoLRIQ as an outcome measure in clinical trials with patients with moderate to severe asthma or COPD. The longitudinal measurement properties in less severe patients still need to be studied.