This subject-masked, randomized, active and placebo-controlled study compared subjects' perceptions of two antibiotic ophthalmic drops. One hundred and twenty-five healthy volunteers received two of the following solutions: moxifloxacin 0.5% ophthalmic solution (Vigamox((R)), Alcon Laboratories, Inc., Ft Worth, TX, USA), azithromycin 1% in DuraSite((R)) (AzaSite(), Inspire Pharmaceuticals, Inc., Durham, NC, USA), or Tears Naturale II((R)) (Alcon Laboratories, Inc., Ft. Worth, TX, USA) in contralateral eyes. Immediately following instillation and at 1, 3, 5, and 10 minutes thereafter, subjects rated comfort, acceptability, and blurring on 0-10 point analog scales stating their preference of treatment. Among subjects receiving moxifloxacin and azithromycin in contralateral eyes, 84% preferred moxifloxacin. Moxifloxacin was rated more comfortable and acceptable with less blurring than azithromycin (p < 0.0001). These differences were observed in both the adult and pediatric populations. Ocular adverse events (redness, irritation, stinging, burning, dryness, itching and chemosis) were observed in 18 (17.3%) eyes receiving azithromycin and 1 (1%) eye receiving moxifloxacin. Moxifloxacin was significantly more tolerable than azithromycin in healthy adult and pediatric eyes. Tolerability and patient acceptance affect compliance; thus these data should be of significance to the clinician.