Purpose To study the incidence of herpetic eye disease (HED) of the ocular surface in diabetics. Design Observational historical cohort study. Setting A district of the largest health maintenance organization in Israel (the Central District of Clalit Health Services). Participants We reviewed the electronic medical records of all patients older than 50 years (159634 patients) in the district, and of these, 22382 (14.0%) patients had diabetes mellitus. Methods All filled prescriptions for acyclovir eye ointment between January 1, 2001 and December 31, 2003 (1483 tubes) and all hemoglobin A 1c laboratory tests during 2003 (41910 tests) were documented. An ocular surface HED event was defined when a patient consumed at least 1 tube of topical acyclovir per month, whereas no acyclovir use was documented 3 months before and 3 months after that event. Main Outcome Measures Incidence of ocular surface HED events in diabetics compared with nondiabetics adjusted for age and gender. Results After age and gender adjustment, significantly more diabetics had ocular surface HED (5.21‰) compared with nondiabetics (4.27‰; P P = 0.05). Diabetics with poor glycemic control (mean annual hemoglobin A 1c > 9%) consumed significantly more ocular acyclovir ( P = 0.01). Multivariate analysis revealed this effect to be independent of age, gender, place of birth, or place of residency. Conclusions Ocular surface HED is significantly more common among patients with diabetes mellitus. Poor glycemic control correlates with increased consumption of ocular acyclovir in diabetic patients.