Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections.