A prospective, double-blind, randomized, placebo-controlled study was performed to evaluate the effect of antibiotic prophylaxis in ear surgery. The present study reports on the results of 750 patients, half of whom received cefuroxime for 1 day, the other half, placebo. All postoperative infections occurring within 2 weeks after the intervention were recorded, together with several preoperative and perioperative parameters. It is concluded that exploratory tympanoplasties (including stapedotomy) and “dry perforation” tympanoplasties should be considered “clean” operations according to the American National Research Council and do not benefit from antibiotic prophylaxis. On the other hand, tympanoplasties performed on draining ears and on ears with cholesteatoma should be considered “dirty” operations for which antibiotic prophylaxis may decrease the postoperative infection rate by factor 3. All postoperative infections healed without sequels under proper treatment, except for three that resulted in graft necrosis-one in the placebo group and two in the cefuroxime group. In consequence, prophylaxis may not be mandatory in the dirty group, although the authors advocate its use for the sake of patient and surgeon comfort.