BACKGROUND Gatifloxacin and moxifloxacin ophthalmic solutions are frequently prescribed for antimicrobial prophylaxis following cataract and corneal refractive surgeries, although the use of topical antibiotics is likely to interfere with wound healing in the immediate postoperative period. A potential factor that may influence rates of wound healing or corneal re-epithelialization is how the solutions are preserved. Gatifloxacin is preserved with 0.005% benzalkonium chloride, whereas moxifloxacin is unpreserved. The purpose of this study was to evaluate the effects of commercially prepared topical gatifloxacin and moxifloxacin on corneal re-epithelialization in rabbit eyes. METHODS In this randomized, prospective, controlled study, 17 New Zealand white rabbits underwent bilateral corneal de-epithelialization procedures using 20% alcohol contained within a 6 mm trephine. Postoperatively, eyes were randomly assigned to receive either gatifloxacin 0.3%, moxifloxacin 0.5%, or balanced salt solution (BSS) four times daily. Each 6 hours during the first 2 days, and every 12 hours thereafter slit-lamp measurements and corneal photography were performed, enabling de-epithelialized surface areas to be calculated via EPCO 2000 computer analysis. RESULTS Gatifloxacin (n = 12) and moxifloxacin (n = 13) treated eyes had a statistically significant (p = 0.036) delay in epithelial healing relative to controls (BSS, n = 8). Healing rates of gatifloxacin and moxifloxacin treated eyes were not significantly different (p = 0.545). CONCLUSIONS We found no significant difference in re-epithelialization rates following topical application of gatifloxacin 0.3% and moxifloxacin 0.5%. Both antibiotic solutions delayed healing compared to BSS. Our analysis suggests that there was no apparent added epithelial toxicity due to the presence of BAK in the gatifloxacin preparation.