OBJECTIVE: To determine if antibiotics improve recovery following tonsillectomy. DATA SOURCES: Electronic databases Medline, Embase, and Cochrane Controlled Trials Register were searched using relevant search terms. Additional trials, if any, were retrieved by searching the references from all identified trials, reviews, correspondences, editorials, and conference proceedings. No language restriction was applied. STUDY SELECTION: Systematic review of trials in which antibiotic was administered as a study medication intraoperatively and/or postoperatively, in children or adults undergoing tonsillectomy or adenotonsillectomy. Only randomized, placebo-controlled, double-blind trials attaining preset quality scores were included. Outcomes analyzed: 1) pain, need for analgesia, fever, halitosis, and return to normal diet and activities; 2) secondary hemorrhage using 2 parameters-significant hemorrhage (ie, warranting readmission, blood transfusion, or return to theatre for hemostasis) and total hemorrhage; and 3) adverse events. RESULTS: Five trials met the eligibility criteria. Antibiotics significantly reduced the number of subjects manifesting fever (relative risk [RR]: 0.62, 95% confidence interval [CI]: 0.45, 0.85) and duration of halitosis (-1.94 [-3.57, -0.30] days), and marginally reduced the time taken to resume normal activity (-0.63 [-1.12, -0.14] days), but had no significant effect in reducing pain scores (-0.01 [-0.60, 0.57]) or need for analgesia. Similarly, there was no significant difference in the time taken to resume normal diet or incidence of significant and total hemorrhage, although data was underpowered to detect differences for these outcomes. In the antibiotic group 4 patients developed an adverse reaction (3 cases of rash and 1 case of oropharyngeal candidiasis), while in the control group 1 patient had an adverse reaction (rash). The RR of antibiotic-related adverse events was 2.45 (0.45, 13.31). CONCLUSION: Antibiotics appear to be effective in reducing some, but not all, morbid outcomes following tonsillectomy, and may increase the risk of adverse events. Further trials are needed to better define the role of antibiotics in facilitating post-tonsillectomy recovery. EBM RATING: A-1a.