Due to the growing cultivation area of genetically modified (GM) maize and the rising number of GM maize varieties commercially available to European farmers, the co-existence between GM and non-GM maize is becoming a burning issue in some European regions.  Hence, Member States are imposing or discussing specific co-existence measures to keep the adventitious presence of GM material in non-GM produces below the established labelling threshold.  As maize is a cross-pollinated crop that uses wind for the dispersal of its pollen, on-farm co-existence measures may rely on the spatial isolation of GM and non-GM maize fields.  In this study, we developed an approach that combines geographic information system (GIS) datasets with Monte Carlo simulations to assess the feasibility of implementing isolation perimeters around GM maize fields, since its practical implementation is rarely addressed in the co-existence debate.  More specifically, five scenarios differing in shares and spatial distributions of GM maize were tested for various isolation perimeters in two agricultural areas in Flanders (Belgium).  The GIS analyses emphasised the small size of maize fields and their scattered distribution throughout the cropped area.  The feasibility of implementing isolation perimeters was largely affected by the (GM) maize share, the spatial distribution of GM maize, and the width of isolation perimeters.  The higher the (GM) maize share and the wider the isolation perimeter, the higher the proportions of farmers with non-GM maize fields occurring within the implemented isolation perimeter.  Compared with randomly distributed GM maize fields, the clustering of GM maize fields on a larger scale and at the farm level increased the feasibility of implementing isolation perimeters.  The approach developed proved to be a valuable tool to quantify the feasibility of implementing isolation perimeters under real agricultural conditions.