Kinetic hydrate inhibitors (KHIs) are chemical substances that prevent gas hydrate plugging of oil and gas production flow lines. The main ingredient in a KHI formulation is one or more water-soluble amphiphilic polymers. We recently presented the first results on the KHI performance of a new class of amphiphilic polymers, namely, poly(2-dialkylamino-2-oxazoline)s, which showed good potential as KHIs. In this work, this class of novel KHIs has been investigated in more detail using both structure I and structure II hydrate-forming gases to optimize the polymer structure for best performance and with higher cloud point temperature for wider field applications. All polymers were tested in high-pressure rocking cells using the slow (1 °C/h) constant cooling test method. The best poly(2-dialkylamino-2-oxazoline)s tested at 2500 ppm contained 5-membered and 6-membered heterocyclic pendant groups and performed similarly to a commercial KHI polymer, poly(