Abstract: The safety and transmutation characteristics of realistic designs of accelerator-driven sub-critical systems (ADS) with various fertile materials were investigated. Either (U,TRU)O2 or (Th,TRU)O2 was loaded in the core. Then the reactor calculations of ADS in steady state were studied using LAHET and MCNP programs, and the coupling system of MCNP and ORIGEN2 was used to calculate the nuclide density evolution with burnup. The results show that ADS loaded with thorium based fuel has the superiority in terms of TRU burning capability, beam current fluctuation, reactivity swing while the other one loaded with uranium based fuel does in terms of the effective delayed neutron fraction and the Doppler effect. From the overall comparison, a core loaded with thorium based fuel is concluded to be better in achieving a long life while maintaining safety and minimizing waste.