The optimal combination of particle and tube size for simulation of a single tube of a wall-cooled multitubular Fischer-Tropsch (FT) reactor with cobalt as catalyst was determined. The maximum size of the tubes, realized without temperature runaway, enhances with increasing particle size until an optimal value is reached, thereby improving the production rate of liquid fuels per tube. Reasons for this are that heat transfer to the cooled tube wall for a given tube size is considerably enhanced by increasing the particle size and that the influence of pore diffusion on the effective rate of FT synthesis gets stronger with rising particle size, which reduces the temperature sensitivity of the reactor and decreases the danger of a temperature runaway. The simulations indicate that the use of FT eggshell catalysts is not an option for fixed-bed reactors. The temperature sensitivity of the reactor is strongly enhanced, which decreases the maximum tube size and with that the productivity per tube. All these effects are valid in general for wall-cooled fixed-bed reactors. Respective criteria are presented.