The peroxide-initiated degradation of polypropylene is simulated by means of a one-dimensional (1D) reactive extrusion (REX) model. Two scale-up rules, namely, constant thermal time and specific energy consumption (SEC) are evaluated for co-rotating intermeshing twin screw extruders (COITSEs) of various sizes. The weight-average molecular weight (Mw) and the polydispersity index (PDI) are selected as the evaluation parameters for testing the scale-up procedures being analyzed. The results for the simulated operating conditions show that when the REX operation is scaled-up under constant thermal time, very good agreement is obtained between the Mw and PDI of the larger extruders and the values of these parameters corresponding to the reference extruder. For the constant SEC approach, more significant variations are observed for both of the aforementioned parameters. In the case of the constant thermal time scale-up approach, the effect of operating conditions of the reference extruder on the scaled-up operation is further analyzed. For a constant screw speed, when the reference mass throughput increases the predicted time of extrusion increases. Regarding the temperature of reaction, the higher increase of this parameter corresponds, in general terms, to the lower mass throughputs and higher screw speeds specified for the reference extruder.