The 1966–1987 Saint Santin/Nançay incoherent scatter radar database is analyzed to determine long-term trends beyond those associated with the “natural” variations of solar and magnetic activity, season, and time of day. Trends averaging some −3 K/yr are found in the F region. Positive trends in the E region may be explained by the subsidence of an overlying warmer regime of air. The trend line seems to change slope around the “breakpoint” year 1979, with the cooling changing from −0.8 K/yr before that time to −5.5 K/yr afterward at 350 km altitude. These trends greatly exceed those predicted by model simulations for increases in greenhouse gas concentrations. Further, carbon dioxide shows no such breakpoint year, but ozone does, near the time of the change in thermospheric trend, and a surface climatic regime shift has also been reported near this time. It is not clear that greenhouse gases are driving the long-term trend in thermospheric temperature. Restriction of analysis to a particular time of day results in greatly different trends, from near zero at midnight to −6 K/yr at noon at 350 km altitude. A separate analysis to determine the long-term trend in the amplitude of the 24 h tide at 350 km altitude shows a large change, with the amplitude diminishing from 136 K in 1966 to 89 K in 1988. Our results show the great need to remove all other natural variations from long-term data sets in determining long-term trends to avoid great ambiguity in trend interpretation.