Background:Despite the strict preventive immunization used in Egypt, Newcastle disease remained a prospective risk to the commercial and backyard chicken industries. The severe economic losses caused by the Newcastle disease virus (NDV) highlight the importance of the trials for the improvement and development of vaccines and vaccination programs. Aim:In the present study, we evaluated the effectiveness of two vaccination schemes for protection against the velogenic NDV (vNDV) challenge. Methods:Four groups (A–D) of commercial broiler chickens were used. Two groups (G–A and G–B) were vaccinated with priming live HB1 GII simultaneously with inactivated GVII vaccines at 5 days of age, then boosted with live LaSota GII vaccine in group A and live recombinant NDV GVII vaccine in group B on day 16. Groups A to C were challenged with NDV/Chicken/Egypt/ALEX/ZU-NM99/2019 strain (10 6 Embryo infective dose 50/0.1 ml) at 28 days of age. Results:Two vaccination schemes achieved 93.3% clinical protection against NDV with body gain enhancement; whereas, 80% of the unvaccinated-challenged birds died. On day 28, the mean HI antibody titers were 4.3 ± 0.33 and 5.3 ± 0.33 log 2 in groups A and B, respectively. As well as both programs remarkably reduced virus shedding. The two vaccination schemes displayed close protection efficacy against the vNDV challenge. Conclusion:Therefore, using the combination of a live attenuated vaccine with an inactivated genetically matched strain vaccine and then boosting it with one of the available live vaccines could be considered one of the most effective programs against current field vNDV infection in Egypt.