To identify the resistance profiles of conjunctival and nasal bacterial isolates in patients undergoing intravitreal injections and to determine if frequent exposures to topical fluoroquinolones increased antimicrobial resistance among these organisms. Prospective cohort study. Patients undergoing intravitreal injection at our institution were enrolled in this study. The conjunctiva and nares of both sides of the patient's face were swabbed and cultured before antiseptic preparation for intravitreal injection. At the time of the study, all patients received 3 days of moxifloxacin eye drops after each intravitreal injection as prophylaxis against endophthalmitis. Resistance to antimicrobials was analyzed using the chi-square test and t test. Two hundred eight conjunctival and nasal specimens were cultured from 104 patients. Forty-two (45%) of 93 patients had at least 1 fluoroquinolone-resistant organism in the nose or conjunctiva. Twelve (48%) of 25 patients with no previous injections had at least 1 resistant organism; 14 (45%) of 31 patients with 1 to 4 previous injections had at least 1 resistant organism; 8 (33%) of 24 patients with 5 to 9 previous injections had at least 1 resistant organism; and 8 (62%) of 13 patients with 10 or more previous injections had at least 1 resistant organism (P = .88; chi-square test, linear by linear association). In this small study, there was no correlation between the number of exposures to topical fluoroquinolones and resistance to fluoroquinolones in nasal and conjunctival flora, but there was a high prevalence of fluoroquinolone resistance among all patient groups.