In late 2016, a highly pathogenic avian influenza (HPAI) virus subtype H5N8 clade 2.3.4.4 was reported in Egypt in migratory birds; subsequently, the virus spread to backyard and commercial poultry in several Egyptian governorates, causing severe economic losses to the poultry industry. Here, a recombinant subunit commercial H5 vaccine prepared from the clade 2.3.2 H5 segment on baculovirus was evaluated in Pekin ducks (Anasplatyrhynchos domesticus) and Muscovy ducks (Cairina moschata) in Biosafety Level 3 isolators by using two vaccination regimes: either a single dose on day 10 and a challenge on day 31 or a double dose on days 10 and 28 and a challenge on day 49. The protection parameters were evaluated after experimental infection with the Egyptian HPAI H5N8 isolate clade 2.3.4.4b (A/common-coot/Egypt/CA285/2016) based on mortality rate, clinical signs, gross lesions, seroconversion, virus shedding, and histopathologic changes. In the single-dose vaccination regime, the mortality rate in Muscovy and Pekin ducks was 10% and 0% vs. 40% and 0% in nonvaccinated challenged ducks, respectively. In the double-dose vaccination regime, the mortality rates in Muscovy and Pekin ducks were 0% and 0% vs. 60% and 40% in nonvaccinated challenged ducks, respectively. Muscovy ducks developed more severe clinical signs and gross lesions than Pekin ducks. In addition, tracheal viral shedding in challenged Muscovy ducks, in the single-dose vaccination regime, was 50%, 22%, and 0% at 3, 5, and 7 days postchallenge (DPC), respectively, and was 0% in all Pekin ducks vs. 100% in all challenged nonvaccinated Muscovy and Pekin ducks at 3, 5, and 7 DPC. The viral shedding in challenged Muscovy and Pekin ducks, in the double-dose vaccination regime, was 0% at 3, 5, and 7 DPC vs. 100% in nonvaccinated challenged Muscovy and Pekin ducks, respectively. The results of this study indicate that the H5 baculovirus-based vaccine can be used in ducks with better vaccination regime based on double-dose vaccination at 10 and 28 days of age. In addition, they highlight the need to evaluate the efficacy of currently used commercial vaccines against challenge with the newly emerged HPAI H5N8 clade 2.3.4.4 in the field in Egypt to ensure proper control strategy in ducks.