During a loss-of-coolant accident (LOCA), the oxide layer grown during normal operations is expected to have a protective effect against high-temperature steam oxidation. However, with respect to post-quench ductility, such a barrier effect may be counterbalanced by a partial dissolution of the pre-oxide layer and associated diffusion of oxygen toward the metal. An extensive study has been carried out on the high-temperature oxidation behavior and post-quench mechanical properties of pre-oxidized Zircaloy-4. Cladding tubes have been pre-oxidized in oxygen environment at 425°C for increasing durations (up to 550 days), leading to pre-oxide layer thicknesses ranging from 7 to 65 μm. All samples have been then subjected to high-temperature steam oxidation at 900°C, 1000°C, or 1200°C followed by water quenching. Metallographic examinations, micro-hardness measurements, mean hydrogen content measurements, ring compression tests, and EPMA oxygen profiles have then been performed. At 900°C and 1000°C, referring to weight gain, the protective efficiency of the pre-oxide layer grown at 425°C appears to depend on its thickness. The protective effect is significant for 20 – to 40-μm pre-oxide thicknesses. Above 40 μm, a partial loss of protectiveness is observed, associated to a significant hydrogen pickup. Thus, mechanical properties of such pre-oxidized claddings are highly degraded compared to an initially bare cladding undergoing a LOCA transient for which post-test ductility is maintained. At 1200°C, at similar oxidation durations, weight gains decrease continuously as the pre-oxide layer thickness increases. Thus, the pre-oxide can be viewed as partially protective; however, post-quench ductility is not improved compared to initially bare claddings.