The effect of kinetic inhibitors, both chemical (PVP and H1W85281) and biological (type III antifreeze protein), on natural gas hydrate formation was investigated using high pressure differential scanning calorimetry (HP-DSC). The presence of inhibitors decreased the overall formation of methane/ethane/propane hydrate compared to systems without added inhibitors. As well, all of the inhibitors significantly delayed hydrate nucleation as compared to water controls. However, the two classes of inhibitors were distinguished by the formation of hydrates with different stabilities. A single hydrate melting peak was seen with the antifreeze protein (AFP), and this was consistent after recrystallization. In contrast, multiple hydrate melting events, some indicating the formation of hydrate structures with high stability, were observed in the presence of the chemical inhibitors, and these varied depending on the crystallization cycle. This heterogeneity suggests that the use of these chemical inhibitors (PVP and H1W85281) may present a special challenge to operators depending upon the gas mixture and environmental conditions and that AFPs may offer a more predictable, efficacious solution in these cases.