Objectives/Hypothesis: The role of prophylactic antibiotics in otologic surgery continues to be debated and perhaps misused. Prior studies have provided conflicting evidence with regard to the benefit obtained from the use of prophylactic antibiotics in surgery for chronic otitis media. The current study was designed to evaluate the role of prophylactic antibiotics in the outcomes of surgery for chronic ear disease. It was the authors' impression that there was no indication for prophylactic antibiotics in such surgery. Study Design: Randomized prospective study performed in a tertiary care facility. Methods: Patients who met inclusion criteria (n = 146) were randomly assigned to an antibiotic treatment group or a control group receiving no prophylactic antibiotics. Patients in the antibiotic treatment group were given preoperative intravenous antibiotics followed by oral antibiotics for 5 days after surgery. Patients were followed postoperatively and observed for clinical evidence of infection and graft failure. Results: There was no statistically significant difference between the two groups with regard to the incidence of postoperative infection or graft survival. Conclusions: The use of prophylactic antibiotics in surgery for chronic ear disease cannot be recommended based on the findings of this study.