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The regional overpower protection (ROP) system of a Canada deuterium uranium (CANDU) reactor was assessed for the direct use of spent pressurized water reactor fuel in CANDU reactors (DUPIC), including the validation of the Winfrith improved multigroup scheme (WIMS)/reactor fuelling simulation program (RFSP)/reduction power (ROVER) code system used for the calculation of the ROP trip setpoint (TSP). Comparative calculations showed that the WIMS/RFSP/ROVER code system produced results consistent with the current design code system for estimating the ROP TSP of the standard natural uranium CANDU reactor. For the DUPIC fuel CANDU core, the ROP TSP was estimated to be 123.4%, which was almost the same as that of the standard natural uranium core. The extra margin of the ROP TSP for the DUPIC fuel system was enhanced by the flattened axial channel power distribution as well as the reduced refueling ripple of the channel power. This study has shown that the DUPIC fuel does not deteriorate the current ROP TSP designed for the natural uranium CANDU reactor.