Wind-driven rain (WDR) effects on the large span retractable roof of a stadium and WDR-induced structural responses are investigated in this paper. The WDR simulations are performed based on the large eddy simulation (LES) method together with the Eulerian multiphase model, and structural responses of the retractable roof subjected to WDR actions are determined by the dynamic analysis of the stadium in time domain. Both mean and instantaneous WDR effects on the roof are presented and discussed. In addition, WDR-induced and wind-induced mean and RMS structural responses are analyzed for comparison purposes. Wind tunnel experimental results of the stadium verify the accuracy of the LES method for estimation of the wind effects on the retractable roof with complex shape in high Reynolds number turbulent flows. The WDR simulation results show that wind phase only has obvious effects on fluctuations of small raindrops. But, rain phase has significant influences on fluctuation of wind phase in the WDR simulation. In view of this, two-way coupled simulation of wind and rain is essential for accurate predictions of WDR. A validation study based on available field measurements of WDR and detailed analysis of the simulation results demonstrates that the numerical method adopted in this paper is an effective tool to predict the WDR effects and WDR-induced responses of a large-scale complex structure.