Abstract: Background Progressive fibrosing interstitial lung diseases (FILD) are associated with high mortality and poor prognosis. However, the factors influencing the progression of FILD have not yet been conclusively established.Objective To identify factors associated with the progression of FILD and develop a corresponding predictive model. Methods This study was a multicenter retrospective study. Clinical data about patients with FILD who were admitted to the Department of Respiratory and Critical Care Medicine at the Fourth, Sixth, and Eighth Medical Centers of Chinese PLA General Hospital from January 1, 2019, to December 31, 2023, were collected. Patients who met the definition of progressive fibrosing interstitial lung diseases (P-FILD) were included in the progression group, while the remaining patients were assigned to the stable group. Baseline clinical data were compared between the progression and stable groups. Variables associated with disease progression were selected using three methods: Lasso regression, multivariate full model logistic regression and multivariate stepwise logistic regression. Receiver operating characteristic (ROC) curves were generated for the latter two multivariate models, and the predictive performance of each model was evaluated and compared. Results A total of 443 patients were included, There were 245 (55.3%) males and 198 (44.7%) females with a mean age of (66.0±11.0) years. There were 215(48.5%) cases in the progressive group, with 123 (57.2%) males and 92 (42.8%) females, a mean age of (66.6±11.1) years. In the stable group, there were 228 cases (51.5%), 122 (53.5%) males and 106 (46.5%) females with a mean age of (65.5±10.8) years. Compared with the stable group, the progressive group had a higher number of patients with smoking history and combined pulmonary hypertension, higher levels of mMRC score, CA19-9, CEA and CA-125, and lower levels of FVC%pred and DLCO%pred, and the difference between the two groups was statistically significant (P<0.05). Multivariate stepwise logistic regression analysis showed that mMRC score of ≥2 (OR=3.533, 95%CI: 1.950 - 6.401), FVC% pred (OR=0.951, 95%CI: 0.935 - 0.967), DLCO% pred (OR=0.942, 95%CI: 0.926 - 0.958), and the presence of pulmonary hypertension (OR=2.745, 95%CI: 1.430 - 5.270) were independently associated with the progression of FILD. These results were consistent with those obtained from multivariate full model logistic regression and lasso regression. The AUC values of the ROC curves for the multivariate full-model regression and multivariate stepwise regression models were 0.844 and 0.840, respectively. Conclusion mMRC score of ≥2, low baseline levels of FVC%pred and DLCO%pred, and the presence of pulmonary hypertension are independently associated with the progression of FILD. Close follow-up and early initiation of antifibrotic therapy should be considered for patients with these factors to reduce the risk of disease progression.