Following the nuclear disaster at Fukushima in Japan in 2011, there is a growing search for novel cladding materials that can displace Zirconium in light water reactors. In this paper, niobium (Nb), titanium (Ti), vana­ dium (Va) and Inconel-600 alloy are selected as possible innovative cladding materials that have high melting points and resist corrosion. MCNPX code was used to simulate these cladding materials in a standard pressurized water reactor assembly. The impact of these materials on the reactor safety aspects was discussed in terms of the depletion calculations at the unit cell and assembly levels. The included reactor safety aspects in this work are effective multiplication factor (Keff), cycle length, relative fission power, reactivity coefficients, reactivity worth, fission products and actinides, neutron spectrum, spectral index, radial power distribution and peaking factor. For each proposed cladding material, the study focused on determining the required thickness (at constant enrichment) and evaluating the suitable enrichment (at constant cladding thickness) to obtain the same cycle length of zirconium. The simulation depicted that the lowest decrease of cycle length was observed for niobium which contributed to reducing the Zirconium cycle length by 15%. Meanwhile, the high absorbing cladding materials such as Ti, Va and Inconel-600 reduced the Zirconium cycle length by 29%, 32% and 40%, respec­ tively. Enhanced negativity of fuel temperature coefficient (FTC), moderator temperature coefficient (MTC) and void reactivity coefficient are noticed for Ti, Va, and Inconel-600 at the BOL. On the other hand, Zr and Nb provide the most negativity of reactivity coefficients at the MOL and EOL owing to the low inventory of Pu-239 and fission products. The control rod worth values of Zr and Nb are larger than those of Ti, Va and Inconel-600 throughout the fuel depletion thanks to the softening of neutron spectrum in the case of Zr and Nb. In terms of minimizing the radioactive waste, Nb offers the second lowest inventory of fission products and actinides after zirconium. Finally, the peaking factors for Inconel-600, Va and Ti are slightly higher than those for Zr and Nb. As a consequence, the power distribution is more controllable in the cases of Zr and Nb.