An evaluation of the temperature and moisture profile retrievals from the Atmospheric Infrared Sounder (AIRS) data is performed using more than 2 years of collocated data sets. The Aqua-AIRS retrievals, global radiosonde (RAOB) measurements, forecast data from the National Center for Environmental Prediction Global Forecasting System (NCEP_GFS), the European Center for Medium Range Forecast (ECMWF), and the operational retrievals from the NOAA 16 satellite Advanced TIROS Operational Vertical Sounder (ATOVS) instrument are used in this validation. Using RAOB observations as the reference, bias and RMS differences are computed for “sea,” “land,” and “all” categories for the AIRS retrievals and other collocated data sets. The results of the intercomparison reveal that temperature and water vapor retrievals from the AIRS are in very good agreement with the RAOBs. The RMS difference for clear-only cases over “sea” and “all” categories is close to the expected goal accuracies, namely, 1°K in 1 km layers for the temperature and better than 15% in 2-km layers for the water vapor in the troposphere. The overall RMS difference for the cloud-cleared cases is also close to the expected product goal accuracy except for a slight degradation at the surface. When AIRS and ATOVS retrievals are compared with the RAOBs, the AIRS temperature retrievals show an improvement over ATOVS of at least 0.5°K for all the accepted cases. Both the ECMWF and the NCEP_GFS forecasts match the RAOB temperatures within 1°K and water vapor within 14%. With respect to biases, the AIRS final retrieval shows a larger bias with the RAOBs relative to ATOVS, NCEP_GFS, and ECMWF. The bias is highly influenced by a larger bias contribution from “land” samples and shows a month-to-month and annual variation that correlates with the CO2 variations. This coupling suggests a need to include CO2 and possibly other trace gas climatologies in the AIRS initial guess to partially mitigate the effects in the final physical retrieval.