Purpose: The authors compare the incidence and clinical course of herpes simplex virus (HSV) keratitis among patients who are positive and negative for human immunodeficiency virus (HIV). Methods: A retrospective cohort study was designed. Outcomes measured in both groups included incidence of HSV keratitis, lesion type (epithelial vs. stromal), lesion location (central vs. peripheral), treatment time, time to first recurrence, and recurrence rate. Results: There was no statistically significant difference between the groups for any of the outcomes measured except for recurrence rate. The recurrence rate was 2.48 times more frequent among patients positive for HIV (1 recurrence per 587 person-days of follow-up among patients positive for HIV vs. 1 per 1455 person-days among patients negative for HIV). Conclusions: Except for recurrence rate, the incidence and clinical course of HSV keratitis in this study were no different among patients positive and negative for HIV.