PVDF hollow fiber membranes with a unique sandwich structure and superior wetting resistance have been designed for vacuum membrane distillation (VMD) of seawater desalination in this study. The sandwich structure consists of two sponge-like inner and outer porous layers and a thin middle layer full of small-size macrovoids. The sponge-like structure in the two porous layers is specially designed because it enhances the mechanical strength of hollow fibers with high wetting resistance. This structure is derived from the spinodal liquid-liquid decomposition during phase inversion. Meanwhile, the middle layer of macrovoids is beneficial for VMD flux because they perform as highways for water transport. Comparing to the large size macrovoids, the small-size macrovoids in PVDF hollow fibers are preferred for VMD applications because they would not significantly reduce the membrane mechanical strength. As a result, the newly developed membranes possess impressively high liquid entry pressures (LEPs) of > 3 bar. This study may provide valuable guidelines in designing next generation PVDF hollow fiber membranes for practical VIVID applications.