Objectives To determine the efficacy of amitriptyline (AMI) in treating irritable bowel syndrome (IBS) in adolescents. Study design Adolescents 12 to 18 years with newly diagnosed IBS were surveyed with a symptom checklist, pain rating scale, visual analog scale, and IBS quality of life (QOL) questionnaire. Subjects were randomized in a double-blinded fashion to receive AMI or placebo, and again completed surveys at 2, 6, 10, and 13 weeks. Results Thirty-three patients (24 female) were enrolled. Patients receiving AMI were more likely to experience improvement from baseline in overall QOL at 6, 10, and 13 weeks (P = .019, .004, and .013). Patients receiving AMI were also more likely to experience a reduction in IBS-associatcd diarrhea at 6 and 10 weeks (P = .029 for both), a reduction in periumbilical Paul at 10 weeks (P = .018), and a reduction in right lower quadrant pain at 6, 10, kind 13 weeks (P = .014, .039, and .004). Conclusion AMI significantly improves overkill QOL in adolescents with IBS and should be a therapeutic option for adolescents with this disorder.