Abstract Infrasound waves generated at Earth’s surface can reach high altitudes before returning to the surface to be recorded by microbarometer array stations. These waves carry information about the propagation medium, in particular temperature and winds in the atmosphere. It is only recently that studies on the assimilation of such data into atmospheric models have been published. Intending to advance this line of research, we here use the modulated ensemble transform Kalman filter (METKF)—commonly used in satellite data assimilation—to assimilate infrasound-related observations in order to update a column of three vertically varying variables: temperature and horizontal wind speeds. This includes stratospheric and mesospheric heights, which are otherwise poorly observed. The numerical experiments on synthetic data but with realistic reanalysis product atmospheric specifications (following the observing system simulation experiment paradigm) reveal that a large ensemble is capable of reducing errors, especially for wind speeds in stratospheric heights close to 30–60 km. While using a small ensemble leads to incorrect analysis increments and large estimation errors, the METKF ameliorates this problem and even achieves error reduction from the prior to the posterior mean estimator. Significance Statement The stratosphere and mesosphere have significantly less observational coverage compared to the troposphere, especially for the winds. This lack of information can reduce the accuracy of medium-range weather forecasts. By mimicking a realistic setup, this study paves the way for including novel observations in the estimation of the atmospheric state in these heights using an ensemble data assimilation method. These observations come from a dataset of opportunity containing infrasound-related measurements that are routinely carried out at several stations around the world.