Stacking of two or more catalyst beds with different activities is an option to increase the maximum productivity in wall-cooled catalytic reactors that are limited by thermal stability. The theory for thermal stability in such reactors for a uniform catalyst activity is well established. However, little work has been done towards a generic criterion for thermal runaway in the case of stacked catalyst beds, for which typically there will be two hot spots rather than just one in the case of a single exothermic nth-order reaction. In the present work, we present a first attempt to extend a classical methodology of constructing runaway boundaries (Barkelew type plots) for the case of two activities, with as additional degrees of freedom the ratio of the two catalyst activities and the dimensionless stacking location. We report novel phase diagrams showing the effect of stacking on the runaway boundaries, i.e. the shift of this boundary as a function of the activity ratio and stacking location. From this, a guideline for optimizing the activity profile emerged: under the constraint of two activities and constant total activity, the maximum lowering of the runaway boundary is obtained when both catalytic zones are equally limiting. Moreover, a dimensionless step location of around 0.55 appears to be optimal, virtually independent of the other dimensionless numbers. The novel “modified Barkelew” plots can be used to quickly assess whether, for a specific application, there may be a benefit in the stacking of catalysts with different activities, to boost the reactor productivity.