The NOAA operational total precipitable water (TPW) anomaly product is available to forecasters to display percentage of normal TPW in real time for applications like heavy precipitation forecasts. In this work, the TPW anomaly is compared to multilayer cloud frequency and vertical structure. The hypothesis is tested that the TPW anomaly is reflective of changes in cloud vertical distribution, and that anomalously moist atmospheres have more and deeper clouds, while dry atmospheres have fewer and thinner clouds. Cloud vertical occurrence profiles from the CloudSat 94-GHz radar and the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) are composited according to TPW anomaly for summer and winter from 2007 to 2010. Three geographic regions are examined: the North Pacific (NPAC), the tropical east Pacific (Niño), and the Mississippi Valley (MSVL), which is a land-only region. Cloud likelihood increases as TPW anomaly values increase beyond 100% over MSVL and Niño. Over NPAC, shallow boundary layer cloud occurrence is not a function of TPW anomaly, while high clouds and deep clouds throughout the troposphere are more likely at higher TPW anomalies. In the Niño region, boundary layer clouds grow vertically as the TPW anomaly increases, and the anomaly range is smaller than in the midlatitudes. In summer, the MSVL region resembles Niño, but boundary layer clouds are observed less frequently than expected. The wintertime MSVL results do not show any compelling relationship, perhaps because of the difficulties in computing TPW anomaly in a very dry atmosphere.