Newcastle disease virus (NDV), an avian virus, is being evaluated for the development of vectored human vaccines against emerging pathogens. Previous studies of NDV-vectored vaccines in a mouse model suggested their potency after delivery by injection or by the intranasal route. We compared the efficacy of various routes of delivery of NDV-vectored vaccines in a non-human primate model. While delivery of an NDV-vectored vaccine by the combined intranasal/intratracheal route elicited protective immune responses, delivery by the subcutaneous route or the intranasal route alone elicited limited or no protective immune responses, suggesting the necessity for vaccine delivery to the lower respiratory tract. Furthermore, direct comparison of a vaccine based on an NDV mesogenic strain (NDV-BC) with a similarly designed NDV vector based on a modified lentogenic strain carrying a polybasic F cleavage site (NDV-VF) suggested that the two NDV strains were similar in immunogenicity and were equally protective.