Newcastle disease virus (
NDV
) is a major threat to the poultry industry worldwide, with a diversity of genotypes associated with severe economic losses in all poultry sectors. Class II genotype VII NDV are predominant in the Middle East and Asia, despite intensive vaccination programs using conventional live and inactivated NDV vaccines. In Egypt, the disease is continuously spreading, causing severe economical losses in the poultry industry. In this study; the protective efficacy of a commercial, inactivated recombinant genotype VII NDV–matched vaccine (KBNP-C4152R2L strain) against challenge with the velogenic NDV strain (Chicken/USC/Egypt/2015) was evaluated in commercial layers. Two vaccination regimes were used; live NDV genotype II (LaSota) vaccine on days 10, 18, and 120, with either the inactivated NDV genotype II regime or inactivated NDV genotype VII–matched vaccine regime on days 14, 42, and 120. The 2 regimes were challenged at the peak of egg production on week 26. Protection by the 2 regimes was evaluated after experimental infection, based on mortality rate, clinical signs, gross lesions, virus shedding, seroconversion, and egg production schedule. The results show that these 2 vaccination regimes protected commercial layer chickens against mortality, but some birds showed mild clinical signs and reduced egg production temporarily. However, the combination of live NDV genotype II and recombinant inactivated genotype VII vaccines provided better protection against virus shedding (20% and 0% vs. 60% and 40%) as assessed in tracheal swabs and (20% and 0% vs. 20% and 20%) in cloacal swabs collected at 3 and 5 D post challenge (
dpc
), respectively. In addition, egg production levels in birds receiving the inactivated NDV genotype VII–matched vaccine regime and in those given inactivated genotype II vaccines were 76.6, 79, 82, and 87.4% and 77.7, 72.5, 69, and 82.5% at 7, 14, 21, and 28 dpc, respectively. The results of this study indicate that recombinant genotype-matched inactivated vaccine along with a live attenuated vaccine can reduce virus shedding and improve egg production in commercial layers challenged with a velogenic genotype VII virus under field conditions. This regime may ensure a proper control strategy in layers.