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In many Italian regions, and particularly in southern Italy, karst aquifers are the main sources of drinking water and play a crucial role in the socio-economic development of the territory. Hence, estimating the groundwater recharge of these aquifers is a fundamental task for the proper management of water resources, while also considering the impacts of climate changes. In the southern Apennines, the assessment of hydrological parameters that is needed for the estimation of groundwater recharge is a challenging issue, especially for the spatial and temporal inhomogeneity of networks of rain and air temperature stations, as well as the variable geomorphological features and land use across mountainous karst areas. In such a framework, the integration of terrestrial and remotely sensed data is a promising approach to limit these uncertainties. In this research, estimations of actual evapotranspiration and groundwater recharge using remotely sensed data gathered by the Moderate Resolution Imaging Spectrometer (MODIS) satellite in the period 2000&ndash, 2014 are shown for karst aquifers of the southern Apennines. To assess the uncertainties affecting conventional methods based on empirical formulas, the values estimated by the MODIS dataset were compared with those calculated by Coutagne, Turc, and Thornthwaite classical empirical formulas, which were based on the recordings of meteorological stations. The annual rainfall time series of 266 rain gauges and 150 air temperature stations, recorded using meteorological networks managed by public agencies in the period 2000&ndash, 2014, were considered for reconstructing the regional distributed models of actual evapotranspiration (AET) and groundwater recharge. Considering the MODIS AET, the mean annual groundwater recharge for karst aquifers was estimated to be about 448 mm∙year&minus, 1. In contrast, using the Turc, Coutagne, and Thornthwaite methods, it was estimated as being 494, 533, and 437 mm∙year&minus, 1, respectively. The obtained results open a new methodological perspective for the assessment of the groundwater recharge of karst aquifers at the regional and mean annual scales, allowing for limiting uncertainties and taking into account a spatial resolution greater than that of the existing meteorological networks. Among the most relevant results obtained via the comparison of classical approaches used for estimating evapotranspiration is the good matching of the actual evapotranspiration estimated using MODIS data with the potential evapotranspiration estimated using the Thornthwaite formula. This result was considered linked to the availability of soil moisture for the evapotranspiration demand due to the relevant precipitation in the area, the general occurrence of soils covering karst aquifers, and the dense vegetation.