Purpose To assess the risk factors for eyes of cataract surgery patients harboring oxacillin-resistant Staphylococcus species on the ocular surface. Setting Ambulatory surgical center, Saint Louis University, Saint Louis, Missouri, USA. Design Prospective in vitro laboratory study of a patient cohort. Methods Conjunctival cultures were obtained on the day of surgery from eyes scheduled for cataract surgery. Patients answered a questionnaire about risk factors that might lead to having oxacillin-resistant Staphylococcus organisms in their eyes. The factors tested were age, sex, race, recent systemic and topical antibiotic usage, recent hospitalization, and exposure to healthcare and institutional settings. Logistic regression analysis was performed. Results Of the 183 eyes cultured, 128 (70.0%) tested positive for Staphylococcus organisms, of which 70 (54.7%) were oxacillin-resistant. Only recent antibiotic usage was statistically significantly associated with the presence of oxacillin-resistant organisms (odds ratio, 8.2; 95% confidence interval, 2.2-30.5; P=.002). The other risk factors were not statistically significantly associated: age (P=.06), sex (P=.33), race (P=.34), recent hospitalization (P=.94), and exposure to healthcare and institutional settings (P=.10). Conclusions Although the nonophthalmic literature has reported various risk factors for the harboring of oxacillin-resistant organisms, in the eyes in this study, only antibiotic usage within 30 days preoperatively was significantly associated with the colonization of oxacillin-resistant organisms on the ocular surface. This finding is important to ophthalmic surgeons when considering perioperative antibiotic prophylaxis. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.