Herpes simplex virus (HSV) infections manifest as recurrent oral or genital mucosal lesions, meningoencephalitis, corneal blindness, and perinatal disease. Subunit vaccines have advanced into the clinic without success. None were tested preclinically in male mice. We compared a single-cycle candidate vaccine deleted in HSV-2 glycoprotein D (ΔgD-2) and subunit gD-2 or gD-1 protein vaccines in a male murine skin model. The ΔgD-2 provided complete protection against 10 times the lethal dose of HSV-1 or HSV-2 clinical isolates, and no latent virus was detected, whereas gD-1- and gD-2-adjuvanted proteins provided little or no protection. Protection correlated with Fc receptor activating but not neutralizing antibody titers.