In our continuing efforts to design nontoxic and biodegradable fuel-system icing-inhibitor (FSII) compounds with improved fuel solubility and anti-icing ability, and nontoxic deicers for aircraft and runways, we describe experimental and molecular modeling efforts that allow us to predict the relative performance of FSII candidates, A small-scale, recirculating simulator containing a mixture of jet fuel, FSII, and water was employed to measure the time needed for the water to freeze and the lowest temperature to be achieved before freezing. The molecular model is based on classical molecular dynamics (MD) simulations of a two component mixture consisting of FSII and water. We assume that anti-icing performance is proportional to the degree of hydrogen bonding between FSIIs and water and, therefore, inversely proportional to the degree of hydrogen bonding between water molecules. FSII performance should therefore increase with decreasing water-cluster size, which is calculated from the MD equilibrium trajectories and defined as the average number of water molecules hydrogen bonded to a given water molecule. A good agreement is found between the theoretical and experimental performance rankings for twelve FSIIs and FSII candidates.