Objective: To elucidate the correlation between two disease-specific severity measures (CPI, composite physiologic index; GAP, gender, age, lung physiology variables) and health-related quality of life in patients with idiopathic pulmonary fibrosis (IPF). Methods: We used data from a previously reported observational cohort study using the Medical Outcome Study Short Form 36 (SF-36) for measuring health-related quality of life. Of the 44 patients with IPF who participated in the initial cross-sectional study, 32 patients participated in the follow-up study. The CPI and the GAP index were calculated at baseline and follow-up. Results: In the cross-sectional study, the CPI only correlated with one SF-36 domain and the GAP index did not correlate with any of the SF-36 domains. In the current longitudinal study (the median follow-up; 14 months), there was a significant increase in both indices: ΔCPI = 11.5 (95% confidence interval; 6.8, 16.1) and ΔGAP index =0.59 (95% confidence interval; 0.25, 0.93). Within-subject changes in the CPI and the GAP index were significantly correlated with those of 5 and 3 subscales of theSF-36, respectively. Declines in 4 subscales of theSF-36 were significantly more severe in subjects whose CPI increased by ≥ 5 than in subjects whose CPI did not. Similarly, declines in 3 subscales were significantly more severe in subjects whose GAP stage increased than in subjects whose GAP stage did not. Conclusion: Serial changes in the CPI and the GAP index may be useful to predict changes in the healthrelated quality of life of IPF patients.