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Factors affecting aviation fuel efficiency are thermal and propulsive efficiencies, and overall drag on aircraft. An along-the-route integration is made for all direct flights in a baseline year, 2010, under current and future atmospheric conditions obtained from 26 climate models under the representative concentration pathway (RCP) 8.5 scenario. Thermal efficiency and propulsive efficiency are affected differently, with the former decreasing by 0.38% and the latter increasing by 0.35%. Consequently, the overall engine efficiency decrease is merely <0.02%. Over the same period, the skin frictional drag increases similar to 3.5% from the increased air viscosity. This component is only 5.7% of the total drag, and the similar to 3.5% increase in air viscosity accounts for a 0.2% inefficiency in fuel consumption. A t test is performed for the multiple-model ensemble mean time series of fuel efficiency decrease for two 20-yr periods centered on years 2010 and 2090, respectively. The trend is found to be statistically significant (p value = 0.0017). The total decrease in aircraft fuel efficiency is equivalent to similar to 0.68 billion gallons of additional fuel annually, a qualitatively robust conclusion, but quantitatively there is a large interclimate model spread.