In data sparse regions, remotely-sensed observations can be used to improve analyses, which in turn should lead to better forecasts. One such source comes from the Atmospheric Infrared Sounder (AIRS), which together with the Advanced Microwave Sounding Unit (AMSU), provides temperature and moisture profiles with an accuracy comparable to that of radionsondes. The purpose of this paper is to describe a procedure to optimally assimilate AIRS thermodynamic profiles—obtained from the version 5.0 Earth Observing System (EOS) science team retrieval algorithm—into a regional configuration of the Weather Research and Forecasting (WRF) model using WRF-Var. The paper focuses on development of background error covariances for the regional domain and background field type, a methodology for ingesting AIRS profiles as separate over-land and over-water retrievals with different error characteristics, and utilization of level-by-level quality indicators to select only the highest quality data. The assessment of the impact of the AIRS profiles on WRF-Var analyses will focus on intelligent use of the quality indicators, optimized tuning of the WRF-Var, and comparison of analysis soundings to radiosondes. The analyses will be used to conduct a month-long series of regional forecasts over the continental U.S. The long-term impact of AIRS profiles on forecast will be assessed against verifying radiosonde and stage IV precipitation data.