Background: Irritable Bowel Syndrome (IBS) is one of the most common gastrointestinal disorders presenting in clinical practice. IBS is a functional bowel disorder in which abdominal pain or discomfort is associated with a change in bowel habit and with features of disordered defecation. Methods: IBS candidates were enrolled in the study using the Rome III diagnostic criteria. Participants were identified as IBS-D (diarrhoea dominant), IBS-C (constipation dominant) as well as an IBS-M (mixed group). The participants were randomly assigned; for intention to treat with 750 mg potentiated clinoptilolite three times daily or placebo. The primary endpoint was to determine whether or not the patient experienced adequate relief of symptoms. Results: At the end of treatment 67% and 40% of patients were classified as overall responders in the potentiated clinoptilolite and placebo groups respectively (N=50). After week three of treatment the number of weekly responders was significantly higher (p=0.048) in the potentiated clinoptilolite group compared to the Placebo group, and at week four of treatment the number of weekly responders was borderline significant higher in the potentiated clinoptilolite group (P=0.06). Secondary endpoints were measured but the population size proved too small to realistically obtain statistical significance (p > 0.5). Conclusion: Potentiated clinoptilolite shows clinical benefit, and should be tested further in larger clinical trials. In addition, potentiated clinoptilolite also shows reduced symptoms of IBD-D and IBS-M respectively. It is recommended that clinical response to dose variation should also be further investigated in designated populations of IBS-M and IBS-D patients.