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Irritable bowel syndrome is the most common disorder diagnosed by gastroenterologists. Although several randomized-controlled trials have assessed the therapeutic role of antidepressant drugs, there is insufficient evidence to support their use.To compare the effects of low-dose amitriptyline in the treatment of diarrhoea-predominant irritable bowel syndrome in a double-blind randomized-controlled trial.Fifty-four patients who fulfilled Rome II criteria for diarrhoea-predominant irritable bowel syndrome were included in this study. Organic causes were ruled out by standard laboratory and radiological tests, and rectosigmoidoscopy. Patients were randomly assigned to receive either 10 mg amitriptyline daily or placebo. Subjects were followed up for 2 months and symptoms were assessed using a questionnaire. Intention-to-treat and per-protocol analysis was performed.Fifty patients completed the study. At 2 months, the amitriptyline group showed greater (P0.05) reduction in the incidence of loose stool and feeling of incomplete defecation. Patients receiving amitriptyline showed greater complete response, defined as loss of all symptoms, compared with those receiving placebo (68% vs. 28%, P = 0.01). Adverse effects were similar between the two groups.Amitriptyline may be effective in the treatment of diarrhoea-predominant irritable bowel syndrome and at low dose is well tolerated.