We conducted a retrospective longitudinal cohort study of 82 penetrating keratoplasties performed to treat herpes simplex keratitis. In 53 cases (65%) there was extensive corneal neovascularization or stromal ulceration and active intraocular inflammation, making the prognosis in these cases poor. Only 32 grafts (39%) were clear at the time of our analysis. Patients with active inflammation, active ulceration, perforation, or extensive neovascularization had particularly poor success rates. Conservative management of perforation before keratoplasty was highly successful (11 clear grafts in 13 eyes [85%]). Other categories with a good prognosis included disciform edema and scarred corneas in quiet eyes. We used a preliminary analysis of the data to build a model to predict the outcome of penetrating keratoplasty in herpes simplex keratitis. The model used preoperative ocular status and management technique as its terms. Testing of the model showed that there were significant differences in outcome between the groups in the sample.