Interpreting stable oxygen isotope (δ18O) records from stalagmites is still one of the complex tasks in speleothem research. Here, we present a novel model-based approach, where we force a model describing the processes and modifications of δ18O from rain water to speleothem calcite (Oxygen isotope Drip water and Stalagmite Model – ODSM) with the results of a state-of-the-art atmospheric general circulation model enhanced by explicit isotope diagnostics (ECHAM5-wiso). The approach is neither climate nor cave-specific and allows an integrated assessment of the influence of different varying climate variables, e.g. temperature and precipitation amount, on the isotopic composition of drip water and speleothem calcite. First, we apply and evaluate this new approach under present-day climate conditions using observational data from seven caves from different geographical regions in Europe. Each of these caves provides measured δ18O values of drip water and speleothem calcite to which we compare our simulated isotope values. For six of the seven caves modeled δ18O values of drip water and speleothem calcite are in good agreement with observed values. The mismatch of the remaining caves might be caused by the complexity of the cave system, beyond the parameterizations included in our cave model. We then examine the response of the cave system to mid-Holocene (6000yr before present, 6ka) climate conditions by forcing the ODSM with ECHAM5-wiso results from 6ka simulations. For a set of twelve European caves, we compare the modeled mid-Holocene-to-modern difference in speleothem calcite δ18O to available measurements. We show that the general European changes are simulated well. However, local discrepancies are found, and might be explained either by a too low model resolution, complex local soil-atmosphere interactions affecting evapotranspiration or by cave specific factors such as non-equilibrium fractionation processes. The mid-Holocene experiment pronounces the potential of the presented approach to analyse δ18O variations on a spatially large (regional to global) scale. Modelled as well as measured European δ18O values of stalagmite samples suggest the presence of a strong, positive mode of the North Atlantic Oscillation at 6 ka before present, which is supported by the respective modelled climate parameters.