Porcine epidemic diarrhea virus (PEDV) infects pigs of all ages but causes severe diarrhea and even death in young nursery piglets, which often results in significant economic losses to the swine industry worldwide. PEDV belongs to the alphacoronavirus genus and is closely related to porcine transmissible gastroenteritis virus (TGEV). PEDV has been adapted to grow in Vero-76 cells (ATCC CRL-1587). Here we describe the ultrastructure and morphogenesis of PEDV in Vero-76 cells. Large vacuoles with stacked membranes are observed and mainly located in the perinuclear space in infected cells. Immature virus particles of different shapes and sizes at different stages of assembly are mostly associated with large vacuoles and arranged in a wheel-like structure. Mitochondria adjacent to the virus-containing vacuoles appear to be swelling and disorganized. Mature viruses with an estimated diameter of 70 nm are mostly dissociated from large vacuoles and diffusely distributed throughout cytoplasm containing dark granular materials. Mature PEDV does not appear to be present in smooth-walled vesicles as described for other coronaviruses. Surface projections or corona-like structures are not apparent in intracellular viruses. Overall, PEDV shows some unique features on ultrastructure and morphogenesis in Vero-76 cells.