Purulent otorrhea is the most common complication of tympanostomy tube (TT) insertion. It may occur in the postoperative period or at any time during the sojourn of the tube. The efficacy of topical antimicrobial prophylaxis against purulent postoperative otorrhea (PPO) has been examined in 5 prospective, randomized studies; all demonstrated a reduction in PPO from topical antimicrobial prophylaxis, but in only 1 study was the difference statistically significant. Because the 5 studies used 2 different experimental designs — By-patient, and by-ear — a single meta-analysis could not be done. However, the by-patient studies met the criteria for meta-analysis, which demonstrated a combined odds ratio of 0.12 (95% confidence interval 0.04 to 0.37, p = .0002). This represents an 85% reduction in otorrhea, which is judged to be clinically as well as statistically significant. We conclude from the available evidence that prophylactic use of topical antimicrobial agents following TT insertion consistently reduces the rate of PPO. However, the low incidence of PPO and the heterogeneity of the published studies prevent making a final judgment for or against the continued use of these agents. Therefore, given that these potentially ototoxic agents are frequently administered to prevent postoperative otorrhea, further study of this subject is warranted. In the meantime, we recommend judicious use of these agents following TT insertion in those cases at higher risk for PPO, namely those with mucoid or purulent effusion.