Ocular issues are common, burdensome, and under-researched among residents of aged care services. This study aims to investigate the prevalence of dry eyes or use of ocular lubricants among residents, and the possible association with systemic medications known or suspected to cause dry eyes. A cross-sectional study of 383 residents of six aged care services in South Australia was conducted. Data were extracted from participants’ medical histories, medication charts, and validated assessments. The main exposure was systemic medications known to cause, contribute to, or aggravate dry eyes. The primary outcome was documented dry eyes or regular administration of ocular lubricants. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between systemic medications and dry eyes/use of ocular lubricants. Dry eyes were documented for 53 (13.8%) residents and 98 (25.6%) residents were administered ocular lubricants. Overall, 116 (30.3%) residents had documented dry eyes/used ocular lubricants. Of these, half (n = 58) were taking a medication known to cause, contribute to, or aggravate dry eyes. Taking one or more medications listed as known to cause dry eyes was associated with having dry eyes/use of ocular lubricants (OR 1.83, 95% CI 1.15–2.94). In sub-analyses, no individual medication was associated with dry eyes/use of ocular lubricants. Dry eyes and use of ocular lubricants are common in residential aged care. Our hypothesis generating findings suggest the need for further research into the clinical significance of systemic medications as a possible cause of dry eyes.