Nipah virus is a highly lethal zoonotic paramyxovirus that was first recognized in Malaysia during an outbreak in 1998. During this outbreak, Nipah virus infection caused a severe febrile neurological disease in humans who worked in close contact with infected pigs. The case fatality rate in humans was approximately 40%. Since 2001, NiV has re-emerged in Bangladesh and India where fruit bats (Pteropus spp.) have been identified as the principal reservoir of the virus. Transmission to humans is considered to be bat-to-human via food contaminated with bat saliva, or consumption of contaminated raw date palm sap, although human-to-human transmission of Nipah virus has also been documented. To date, there are no approved prophylactic options or treatment for NiV infection. In this study, we produced mammalian cell-derived native Nipah virus-like particles composed of Nipah virus G, F and M proteins for use as a novel Nipah virus vaccine. Previous studies demonstrated that the virus-like particles were structurally similar to authentic virus, functionally assembled and immunoreactive. In the studies reported here, purified Nipah virus-like particles were utilized either alone or with adjuvant to vaccinate golden Syrian hamsters with either three-dose or one-dose vaccination regimens followed by virus challenge. These studies found that Nipah virus-like particle immunization of hamsters induced significant neutralizing antibody titers and provided complete protection to all vaccinated animals following either single or three-dose vaccine schedules. These studies prove the feasibility of a virus-like particle-based vaccine for protection against Nipah virus infection.