Introduction: Airway reopening involves pressure-driven propagation and rupture of liquid plugs that obstruct airways during coughing or mechanical ventilation. Most numerical studies assume rigid airway walls and neglect airway deformation, although deformation occurs under both healthy and diseased conditions. We hypothesize that airway wall compliance alters plug propagation and rupture through changes in pressure and wall shear stress (WSS). The objective of this study is to develop a fluid-structure interaction (FSI) framework to quantify the mechanical effect of airway wall compliance. Methods: A multiphase FSI model was developed in OpenFOAM to capture the air-mucus interface, coupled to a deformable airway wall solved in CalculiX through preCICE. A range of airway wall thicknesses and mucus viscosities representative of healthy and COPD conditions was tested. Results are presented for a representative case (μ = 1000 cP, wall thickness = 1.4 mm, airway radius = 2 mm) [2,3]. Liquid plug propagation under the same imposed pressure drop was simulated for both rigid and deformable airway walls. The capillary number was computed using plug speed. Rupture time, peak pressure, pressure area under the curve (AUC), peak WSS, and WSS AUC were evaluated at the instant before rupture. Results: For the representative case, airway wall compliance led to an earlier plug rupture, with a rupture time 11% shorter than in the rigid-wall model, while operating at similar capillary numbers (Ca ≈ 27-32). Close to rupture, the deformable airway showed a 7% increase in peak pressure, while the pressure AUC decreased by about 14%. Wall shear stress was reduced in the deformable case, with a 7% decrease in peak WSS and a 25% reduction in WSS AUC. These results demonstrate that airway wall compliance significantly changes pressure and shear stress distributions during airway reopening, and deformation should be accounted for in airway reopening models. References: [1]: Fujioka H., Takayama S., Grotberg J.B. Unsteady propagation of a liquid plug in a liquid-lined straight tube. Phys. Fluids, 20, 062104 (2008). [2]: Lu W., Zheng J. The function of mucins in the COPD airway. Curr. Respir. Care Rep., 2, 155–166 (2013). [3]: Weikert T. et al. Automated quantification of airway wall thickness on chest CT using retina U-Nets. Eur. J. Radiol., (2020).