In this chapter, we analyse the influence of the Carpathian Mountains on the variability of stable isotopes in precipitation by employing a combination of observed and model data. Overall, the mean value of the stable isotopes in precipitation over the Carpathian Mountains, based on observational data, was −9.8‰ for δ18O and −68.6‰ for δ2H. The local meteoric line, using all samples from the study sites, was δ2 H = 7.65 × δ18 O + 5.82. The simulated δ18 O, based on the ECHAM5-wiso isotopes enable model, showed good agreement with the observed isotopic data. By comparing all the monthly values of the observed isotopic data from all analysed stations and the corresponding model data, a correlation coefficient of 0.76 (n = 455, p, 0.001) was obtained. The spatial distribution of the simulated δ18O values in precipitation had the lowest values over the Romanian Carpathian Mountains and the highest values over the extra-Carpathian area, with the maximum in southeastern Romania. This pattern was strongly influenced by the Carpathian Mountains orography. Using the simulated δ18 O data, we show that the spatial distribution of the δ18O values increases with temperature and decreases with altitude and latitude (−0.5‰ for δ18O per degree of latitude). The continental gradient is characterized by a polynomial trend of the second degree in the form of a large-open ‘U’ shape, and the general pattern of the δ18 O values follows the spatial distribution of the Carpathian Mountains.