Stable isotopes in precipitation are recognized as a major tool for tracking the water cycle. The development of gridded datasets is a solution to the need for high-resolution isotopic data. The lack of measurement though, dictates the use of “long-term average” isotopic values, usually, calculated from short time series, of unequal durations and, sometimes, not even referring to the same time period. Thus, the influence of possible trends, that might be present in the isotopic data, should be accounted for. In the present work, we investigated the existence of temporal trends in the isotopic composition of precipitation of central Europe and eastern Mediterranean. Nine stations were selected, having time series extending over at least a 20-year-long period and fulfilling certain data completeness criteria. Possible trends were detected for three overlapping 20-year periods (1961–1980, 1971–1990, and 1981–2000) using linear regression, the Mann–Kendall test, and a partial Mann–Kendall test, to compensate for the influence of meteorological parameters. We found that very few cases present statistically significant trends. There is significant variability of the observed trends, both on a seasonal and on a station basis, in the central Europe and the eastern Mediterranean area alike. Overall, the insignificance of the observed isotopic trends, and the lack of any coherent spatial and temporal patterns, seems to be supporting the current practice for estimating the long-term average isotopic composition of precipitation.