The solution hydration behavior of a series of lactam-based kinetic clathrate hydrate inhibitors (KHIs) has been studied in order to determine mechanistic insight into their KHI performance. IR and 1H NMR spectroscopic titration data were compared across a series of mono- and bis(lactam) model compounds, and solid-phase hydration behavior was examined by dynamic vapor sorption. The structures of several of the model compounds have been investigated by X-ray crystallography. The work reveals insight into the very low crystallinity and high hygroscopicity of these materials which is linked to their performance as KHIs. Analysis of water binding in sour gas systems, containing H2S and CO2, reveals no effect on the water affinity of the lactams, suggesting that sour gas components do not inhibit KHI performance, but rather promote clathrate hydrate formation.