Calibration of satellite observations is crucial for ensuring the quality of retrieved products essential for meteorological and climate applications. Calibration is obtained and monitored through a cascade of stages, including postlaunch vicarious calibration/validation activities through comparison with independent reference measurements. Here, the vicarious calibration method using radiative transfer simulations based on reference radiosondes is considered in the framework of the calibration/validation activities for the Microwave Imager (MWI) and the Ice Cloud Imager (ICI) to be launched with the Second Generation of the EUMETSAT Polar System. This paper presents an overview of the uncertainty characterizing the vicarious calibration of MWI and ICI using radiosondes as performed within the EUMETSAT-funded VICIRS study. The uncertainty characterization is pursued following a metrological approach, providing a preliminary estimation of all the identified sources. The same approach is used to develop a rigorous method for estimating the number of comparison pairs (i.e., observations vs. simulations) needed to reach a certain level of accuracy in bias determination.