We conducted a prospective, randomized, controlled, double-blind study of 33 patients to compare the efficacy and tolerability of a new glycerin formulation of ototopical 0.3% ciprofloxacin with that of a conventional aqueous formulation of ciprofloxacin for the treatment of acute external otitis. Outcomes measures were resolution of discharge, swelling, pain, and redness and the incidence of adverse side effects. Patients were examined on three occasions: on the day of enrollment (visit 1), 48 to 72 hours later (visit 2), and 7 days after enrollment (visit 3). At visit 2, the patients in the glycerin group showed a significantly greater resolution of discharge. We observed the same pattern with respect to swelling, pain, and redness, which resolved more quickly in the glycerin group, although not significantly so. All patients were cured by visit 3, and the two treatments were equally well tolerated. On the basis of our findings, we conclude that the glycerin formulation of ototopical 0.3% ciprofloxacin appears to be at least as effective as the aqueous form in the treatment of acute external otitis-and in the case of otorrhea, more so.