New zirconium oxide (ZrO2)-based organic-inorganic multilayers were fabricated and tested for flexible moisture barriers and compared with typical aluminum oxide (Al2O3)-based multilayers. We report that amorphous ZrO2 had a better intrinsic barrier property than that of amorphous Al2O3. Due to the lower elastic modulus of ZrO2, the ZrO2-based structures had better flexibility than that of the Al2O3-based structures. The ZrO2-based barrier was superior to the Al2O3-based barrier not only for flexibility but also for barrier performance. The barrier property and flexibility of the ZrO2-based structures were enhanced by about 20% and 30% over those of the Al2O3-based structures, respectively.