The synergistic effect of a range of solvents on the kinetic hydrate inhibitor (KHI) performance of poly(N-isopropyl methacrylamide) (PNIPMAm) has been investigated in slow (ca. 1 degrees C/h) constant cooling high-pressure (76 bar) rocking cell experiments using a structure II forming synthetic natural gas mixture. We have tested the synergistic effects of several monoglycol ethers and compared them to those of corresponding diglycol ethers and alcohols. Compounds containing lactate, carboxylate, ammonium, and pyrrolidone headgroups have also been investigated as synergists. In general the monoglycol ethers were found to function best as synergists with PNIPMAm, and the performance improved going from n-butyl to isobutyl, cyclopentyl, and cyclohexyl alkyl substituents. The best performing synergist in this study was found to be 2-(cyclohexyloxy)ethanol (CHexGE). Addition of 5000 ppm CHexGE to 2500 ppm PNIPMAm-II (made in isopropyl alcohol and precipitated out, M-n = 8100 g/mol) dropped T-o from 6.8 degrees C for pure polymer to the situation where no hydrate formation occurred in 9 out of 10 experiments down to 2 degrees C, the minimum test temperature and a subcooling of 17.3 degrees C. PNIPMAm identically made with similar molecular weight and kept in n-butyl glycol ether (nBGE), isobutyl glycol ether (iBGE), and tertbutyl glycol ether (tBGE) reaction solvents gave similar performances as KHIs. The performance of PNIPMAm sometimes varied depending on whether the polymer was made and kept in synergist solvent, or synergist was added to the isolated polymer. For example, nBGE added to pure PNIPMAm performed worse than PNIPMAm made in nBGE, even when the polymer molecular weights were similar. In contrast, PNIPMAm made in iBGE gave a performance similar to that of iBGE added to pure PNIPMAm. The seawater biodegradability according to the 28 day OECD306 test protocol is reported for some of the solvents tested for synergism. In particular, the high flash point solvent n-butyl lactate was found to be readily biodegradable. Combined with a reasonable effect as synergist with PNIPMAm, this makes n-butyl lactate a component to consider when developing more environmentally friendly KHI formulations.