Summary The coordinated operation of reservoirs in large-scale river basins has great potential to improve flood mitigation. However, this requires large scale hydrological models to translate the effect of reservoir operation to downstream points of interest, in a quality sufficient for the iterative development of optimized operation strategies. And, of course, it requires reservoirs large enough to make a noticeable impact. In this paper, we present and discuss several methods dealing with these prerequisites for reservoir operation using the example of three major floods in the Bavarian Danube basin (45,000 km2) and nine reservoirs therein: We start by presenting an approach for multi-criteria evaluation of model performance during floods, including aspects of local sensitivity to simulation quality. Then we investigate the potential of joint hydrologic-2d-hydrodynamic modeling to improve model performance. Based on this, we evaluate upper limits of reservoir impact under idealized conditions (perfect knowledge of future rainfall) with two methods: Detailed simulations and statistical analysis of the reservoirs’ specific retention volume. Finally, we investigate to what degree reservoir operation strategies optimized for local (downstream vicinity to the reservoir) and regional (at the Danube) points of interest are compatible. With respect to model evaluation, we found that the consideration of local sensitivities to simulation quality added valuable information not included in the other evaluation criteria (Nash–Sutcliffe efficiency and Peak timing). With respect to the second question, adding hydrodynamic models to the model chain did, contrary to our expectations, not improve simulations, despite the fact that under idealized conditions (using observed instead of simulated lateral inflow) the hydrodynamic models clearly outperformed the routing schemes of the hydrological models. Apparently, the advantages of hydrodynamic models could not be fully exploited when fed by output from hydrological models afflicted with systematic errors in volume and timing. This effect could potentially be reduced by joint calibration of the hydrological–hydrodynamic model chain. Finally, based on the combination of the simulation-based and statistical impact assessment, we identified one reservoir potentially useful for coordinated, regional flood mitigation for the Danube. While this finding is specific to our test basin, the more interesting and generally valid finding is that operation strategies optimized for local and regional flood mitigation are not necessarily mutually exclusive, sometimes they are identical, sometimes they can, due to temporal offsets, be pursued simultaneously.