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The 486m-long roof of Shenzhen Citizens Centre is one of the world’s longest spatial lattice roof structures. A comprehensive numerical study of wind effects on the long-span structure is presented in this paper. The discretizing and synthesizing of random flow generation technique (DSRFG) recently proposed by two of the authors (Huang and Li 2008) was adopted to produce a spatially correlated turbulent inflow field for the simulation study. The distributions and characteristics of wind loads on the roof were numerically evaluated by Computational Fluid Dynamics (CFD) methods, in which Large Eddy Simulation (LES) and Reynolds Averaged Navier-Stokes Equations (RANS) Model were employed. The main objective of this study is to explore a useful approach for estimations of wind effects on complex curved roof by CFD techniques. In parallel with the numerical investigation, simultaneous pressure measurements on the entire roof were made in a boundary layer wind tunnel to determine mean, fluctuating and peak pressure coefficient distributions, and spectra, spatial correlation coefficients and probability characteristics of pressure fluctuations. Numerical results were then compared with these experimentally determined data for validating the numerical methods. The comparative study demonstrated that the LES integrated with the DSRFG technique could provide satisfactory prediction of wind effects on the long-span roof with complex shape, especially on separation zones along leading eaves where the worst negative wind-induced pressures commonly occur. The recommended LES and inflow turbulence generation technique as well as associated numerical treatments are useful for structural engineers to assess wind effects on a long-span roof at its design stage.