Background: Antifbrotic therapy can slow disease progression (DP) in patients with idiopathic pulmonary fbrosis (IPF). However, the prognostic biomarkers for DP in patients with IPF receiving antifbrotic therapy have not been identifed. Therefore, we aimed to evaluate the prognostic efcacy of serum Krebs von den Lungen-6 (KL-6) for DP in patients with IPF receiving antifbrotic therapy. Methods: The clinical data of 188 patients with IPF who initiated antifbrotic therapy at three tertiary hospitals was retrospectively analyzed. DP was defned as a relative decline in forced vital capacity (FVC)≥10%, difusing capacity for carbon monoxide≥15%, acute exacerbation, or deaths during 6 months after antifbrotic therapy. Results: The mean age of patients was 68.9 years, 77.7% were male, and DP occurred in 43 patients (22.9%) during follow-up (median, 7.6 months; interquartile range, 6.2?9.8 months). There was no diference in baseline KL-6 levels between the DP and no-DP groups; however, among patients with high baseline KL-6 levels (≥500 U/mL), changes in KL-6 levels over 1 month were higher in the DP group than those in the non-DP group, and higher relative changes in KL-6 over 1 month were independently associated with DP (odds ratio, 1.043; 95% confdence interval 1.005?1.084) in the multivariable logistic analysis adjusted for age and FVC. In the receiver operating characteristic curve analysis, the 1-month change in KL-6 was also useful for predicting DP (area under the curve=0.707; P