We present ground-based microwave measurements of mesospheric water vapor made by the Water Vapor Millimeter-wave Spectrometer (WVMS) instruments since the early 1990s from sites in California, Hawaii, and New Zealand. These measurements are compared with coincident measurements from the Halogen Occultation Experiment, the Aura Microwave Limb Sounder, and Sounding of the Atmosphere using Broadband Emission Radiometry; all of which combine to cover the entire time period of the ground-based measurements. Comparisons are presented both on ∼weekly timescales in order to better identify discontinuities in the relative differences and on annual timescales in order to better study geophysical variations. The WVMS retrievals shown here are available on the Network for the Detection of Atmospheric Composition Change database. The range of WVMS trends and the differences from the satellite trends, with the latter varying over a range of ∼3%/decade, provide an estimate of how accurately it would be possible to determine multidecadal trends using ground-based microwave instruments in a postsatellite era. This uncertainty is comparable to the trend in mesospheric water vapor that is expected to have occurred since the early 1990s. Plain Language Summary Understanding long-term trends in water vapor in the middle atmosphere (the atmosphere from about 20 to 80 km) is important because increases in water vapor can cause additional ozone depletion and there are indications that variations in middle atmospheric water vapor may affect global surface climate. Increases in water vapor in the middle atmosphere are caused by increasing anthropogenic methane emissions, but changes are also caused by other factors, such as variations in tropical tropopause (the boundary that separates the troposphere from the stratosphere) temperatures. These temperatures are important because as air moves upward from the troposphere to the stratosphere the very cold temperatures at the tropopause freeze dry most of the water from the rising air. This study focuses on ground-based microwave spectrometers that have been measuring water vapor in the middle atmosphere from three sites since the early 1990s. We provide both an estimate of the trend since then and, based on comparisons with satellite data, an estimate of the uncertainty of the trend from these ground-based instruments. Understanding the uncertainty of this trend is important given the unfortunate likelihood that satellite measurements of middle atmospheric water vapor will be unavailable in future decades.