A performance comparison is made between a Random Packed Bed (RPB) and a Packed Closed Cross Flow Structure (CCFS) reactor model for the Fischer-Tropsch Synthesis. The model incorporates an earlier reported reaction-diffusion catalyst model with chain growth probability depending on the local conditions. 180,000 full reactor simulations have been performed for an extensive parameter space exploration to determine optimal sets of parameters at the maximum Space Time Yield of C5+ products. Results show that particles sizes tend to be minimized and the optimal inlet syngas ratio is relatively low (similar to 1). This study demonstrates the limitations of the RPB reactor at higher catalyst activities and shows the potential of the Packed CCFS reactor as an alternative. At catalyst activities of 3 times that reported by Yates-Satterfield the performance at optimal conditions of the Packed CCFS is 12% lower than RPB. At 10 times the YS activity the RPB takes relatively little advantage of the more active catalyst, productivity only increases by 24% compared to optimum conditions at 3 times YS activity. The Packed CCFS, on the other hand, is able to increase reactor productivity with 63% compared to its optimized benchmark conditions at 3 times YS activity. In spite of its lower catalyst inventory, the Packed CCFS can benefit from higher catalyst activities due to its improved heat transport properties and higher catalyst effectiveness at similar pressure drop over the reactor. Furthermore, larger reactor diameters can be applied with limited impact on the productivity per reactor volume. (C) 2015 Elsevier B.V. All rights reserved.