The aim of our study was to assess in our context, the efficacy of Rifaxim in improving the symptoms of irritable bowel syndrome particularly in its diarrheal (IBS-D) or mixed (IBS-DC) component and therefore assess its impact on patients’ quality of life. Patients and methods: This was an uncontrolled, non-comparative prospective cohort study of a single group of patients. Patients recruitment was done in two University Hospitals for 6 months (September 2015-February 2016). Were included ambulatory patients, male or female, aged 18 - 75 years, with diarrheic IBS (IBS-D) or mixed IBS (IBS-DC) diagnosed according to Rome III criteria and who agreed to participate in the study. Each patient received 400mg Rifaximin × 2/d for 15 days. The overall assessment of the efficacy of treatment at D15 (end of treatment) and D30 (2 weeks post-treatment) was the primary criterion of judgment. The statistical tests used were the Chi-square test and Fisher’s exact test for the qualitative variables and Student’s test for the quantitative variables. Results: A total number of 30 patients (16 women) with an average age of 44.5 ± 13.9 years were included. The overall assessment of symptoms by the patient with the Likert scale found 28 (93.3%) patients, 12 (40%) patients and 10 patients (33.3%) for a scale ≥2 at D0, D15 and D30 respectively. The assessment of the intensity of pain or abdominal discomfort found at D0, D15 and D30 respectively: 27(90%), 13(43.4%) and 6(20.1%) patients who had an EVA score > 2. The mean score for Francis to assess the improved quality of life was 247.1 ± 97.4 at D0, 99.8 ± 63.1 at D15 and 128.8 ± 70.6 at D30. Conclusion: There is a good overall improvement of symptoms in our patients suffering from IBS-D or mixed (IBS-DC) on Rifaximin with improvement of the quality of life.