During geothermal reservoir development, drilling deep boreholes turns out to be extremely expensive and risky. Thus, it is of great importance to work out the details of suitable borehole locations in advance. Here, given a set of existing boreholes, we demonstrate how a sophisticated numerical technique called optimal experimental design helps to find a location of an additional exploratory borehole that reduces risk and, ultimately, saves cost. More precisely, the approach minimizes the uncertainty when deducing the effective permeability of a buried reservoir layer from a temperature profile measured in this exploratory borehole. In this paper, we (1) outline the mathematical formulation in terms of an optimization problem, (2) describe the numerical implementation involving various software components, and (3) apply the method to a 3D numerical simulation model representing a real geothermal reservoir in northern Italy. Our results show that optimal experimental design is conceptually and computationally feasible for industrial-scale applications. For the particular reservoir and the estimation of permeability from temperature, the optimal location of the additional borehole coincides with regions of high flow rates and large deviations from the mean temperature of the reservoir layer in question. Finally, the presentation shows that, methodologically, the optimization method can be generalized from estimating permeability to finding any other reservoir properties.