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This paper describes a procedure to assimilate Atmospheric Infrared Sounder (AIRS)-retrieved thermodynamic profiles into a regional configuration of the Weather Research and Forecasting (WRF) model and validates subsequent precipitation forecasts over the eastern half of the continental U.S. Quality indicators were used to select the highest quality temperature and moisture profiles for assimilation throughout the entire atmosphere in clear and partly cloudy regions and above cloud top in cloudy regions. Separate error characteristics for land and water profiles were also used in the assimilation process. Assimilation of AIRS profiles produced analyses with a better validation to in situ observations than the short-term WRF forecast first-guess field. The AIRS-enhanced initial conditions improved simulation of a severe weather event over Texas and Louisiana from February 12-13, 2007. For this event, assimilation of AIRS profiles produced a more unstable boundary-layer air mass in the warm sector ahead of an advancing midlatitude cyclone, resulting in enhanced convective available potential energy in the model. The simulated squall line and precipitation totals from a forecast initialized with AIRS-enhanced initial conditions more closely reflected ground-based observations than one initialized with a no-AIRS control forecast. The impact of the improved initial conditions through the assimilation of AIRS profiles was further demonstrated through an evaluation of a 37-day period from the winter of 2007. The unstable environment over the Gulf of Mexico and coastal region with the AIRS-enhanced initial conditions resulted in 20%+ improvements in the 6-h accumulated precipitation forecasts out to 48 h over that period.