To compare the rate of epithelial healing following photorefractive keratectomy (PRK) with two commercially available fourth-generation fluoroquinolones, gatifloxacin (Zymar, Allergan, Irvine, California) and moxifloxacin (Vigamox, Alcon Laboratories, Fort Worth, Texas).Double-masked, randomized, prospective trial.Thirty-five subjects received gatifloxacin in one eye and moxifloxacin in the fellow eye following PRK with a 9.0-mm epithelial defect. Patients were examined daily after surgery until the epithelium had healed completely in both eyes. Beginning on post-operative day 3, photos were taken and used to confirm epithelial healing or measure the area of residual epithelial defects. Healing times and defect sizes were compared using the Wilcoxon signed-ranks test.Both eyes healed on the same day in 18 of the 35 subjects (51.4%). In 13 of 35 (37.1%) subjects, the moxifloxacin-treated eye healed first, compared with only four of 35 (11.4%) subjects whose gatifloxacin-treated eye healed first. All six of the eyes that took 2 days longer than their fellow eye to heal were gatifloxacin-treated. Median healing time for both groups was 4 days (moxifloxacin range: 3 to 7 days; gatifloxacin range: 3 to 9 days; P = .01), but only 69% of gatifloxacin-treated eyes had healed by day 4 compared with 80% of the moxifloxacin-treated eyes. Overall, on each post-operative day, defect sizes were greater for the gatifloxacin-treated eyes. This difference was statistically significant on day 4 (P = .027).Eyes treated with moxifloxacin healed faster and had smaller defects compared with those treated with gatifloxacin. This provides another factor to consider in selecting antibiotic prophylaxis for corneal refractive surgery.