Objective: Tonsillectomy is one of the most common pediatric surgical procedures performed in the United States. The postoperative period can be particularly painful, and there is currently no consensus on an optimal analgesic regimen. The objective of this study was to evaluate efficacy and safety of the single drug tramadol versus codeine/acetaminophen post-tonsillectomy. Design: Prospective, double-blinded, randomized controlled trial. Setting: Large, Midwestern US pediatric hospital. Patients: Eighty-four children aged 4-15 years who underwent a tonsillectomy (with or without adenoidectomy) procedure were randomized and 74 were included in the analysis. Interventions: Group 1 received liquid codeine/acetaminophen for 10 days posttonsillectomy (5 days scheduled, followed by 5 days as-needed). Group 2 received liquid tramadol for 10 days post-tonsillectomy (5 days scheduled, followed by 5 days as-needed). Main outcome measures: Efficacy and side effects were evaluated using a 10-day take-home diary that was completed by parents. Results: Children in both study arms reported adequate post-tonsillectomy pain management without significant differences between groups in pain scores. Oversedation was significantly higher on the day of surgery in the codeine/acetaminophen group, and itching was experienced by significantly more children in the tramadol group during the postoperative period. Conclusions: As part of multimodal analgesia, scheduled plus as-needed tramadol may be considered for children in the postoperative setting due to its analgesic properties, low potential for side effects, and good safety profile.