Vinyl lactam-based polymers have been shown to be excellent kinetic hydrate inhibitors (KHIs), inhibiting the formation and growth of methane hydrate under low subcooling conditions. However, under moderate/high subcooling conditions, they lose their inhibitory effect and can even be converted into hydrate promoters. In this work, molecular dynamics simulations were employed to explore the invalidation mechanism of two vinyl lactam-based KHIs, namely, PVP-A and PVP, under high subcooling conditions. By analyzing the nucleation and growth trajectories of methane hydrate in the absence/presence of KHIs, we found that the addition of KHIs could shorten the nucleation time of methane hydrate by reducing the mass transfer resistance of methane and water molecules and accelerating the formation of the hydrate precursor. Additionally, KHIs can facilitate the formation and survival of sII hydrate by improving the kinetic superiority of the methane-water homogeneous solution. (C) 2019 Elsevier Ltd. All rights reserved.