We detail the development of a flexible simulation program (NMR_DIFFSIM) that solves the nuclear magnetic resonance (NMR) spin diffusion equation for arbitrary polymer architectures. The program was used to explore the proton (H-1) NMR spin diffusion behavior predicted for a range of geometrical models describing polymer exchange membranes. These results were also directly compared with the NMR spin diffusion behavior predicted for more complex domain structures obtained from molecular dynamics (MD) simulations. The numerical implementation and capabilities of NMR_DIFFSIM were demonstrated by evaluating the experimental NMR spin diffusion behavior for the hydrophilic domain structure in sulfonated Diels-Alder Poly(Phenylene) (SDAPP) polymer membranes. The impact of morphology variations as a function of sulfonation and hydration level on the resulting NMR spin diffusion behavior were determined. These simulations allowed us to critically address the ability of NMR spin diffusion to discriminate between different structural models, and to highlight the extremely high fidelity experimental data required to accomplish this. A direct comparison of experimental double-quantum-filtered H-1 NMR spin diffusion in SDAPP membranes to the spin diffusion behavior predicted for MD-proposed morphologies revealed excellent agreement, providing experimental support for the MD structures at low to moderate hydration levels. (c) 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 62-78