Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir following corneal transplantation for herpes simplex keratitis was compared to that in nine patients (9 eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without receiving postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared to a 44% (4/9) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01).="" graft="" failure="" occurred="" in="" 14%="" (2/14)="" of="" acyclovir="" treatment="" eyes="" and="" in="" 56%="" (5/9)="" of="" the="" grafts="" in="" patients="" not="" receiving="" acyclovir.="" long="" term="" prophylactic="" oral="" acyclovir="" significantly="" decreased="" the="" recurrence="" of="" herpes="" simplex="" keratitis="" and="" reduced="" corneal="" graft="" failure="" in="" patients="" with="" a="" history="" of="" recurrent="" herpes="" simplex="" keratitis="" who="" underwent="" corneal="">