The Middle Miocene (15.99 to 11.65 Ma) of Europe witnessed major climatic, environmental, and vegetational change, yet we are lacking detailed reconstructions of Middle Miocene temperature and precipitation patterns over Europe. Here, we use a high-resolution (∼0.75°) isotope-enabled general circulation model (ECHAM5-wiso) with time-specific boundary conditions to investigate changes in temperature, precipitation, and δ18O in precipitation (δ18Op). Experiments were designed with variable elevation configurations of the European Alps and different atmospheric CO2 levels to examine the influence of Alpine elevation and global climate forcing on regional climate and δ18Op patterns. Modeling results are in agreement with available paleobotanical temperature data and with low-resolution Middle Miocene experiments of the MioMIP1 project. However, simulated precipitation rates are 300 - 500 mm/year lower in the Middle Miocene than for pre-industrial times for central Europe. This result is consistent with precipitation estimates from herpetological fossil assemblages, but contradicts precipitation estimates from paleobotanical data. We attribute the Middle Miocene precipitation change in Europe to shifts in large-scale pressure patterns in the North Atlantic and over Europe and associated changes in wind direction and humidity. We suggest that global climate forcing contributed to a maximum δ18Op change of ∼2‰ over high elevation (Alps) and ∼1‰ over low elevation regions. In contrast, we observe a maximum modeled δ18Op decrease of 8‰ across the Alpine orogen due to Alpine topography. However, the elevation-δ18Op lapse rate shallows in the Middle Miocene, leading to a possible underestimation of paleotopography when using present-day δ18Op - elevation relationships data for stable isotope paleoaltimetry studies.