Abstract: Objective: To evaluate efficacy and safety of Medilac-S (Bacillus subtilis and Enterococcus faecium) and BIFICO (Bifidobacterium longum, lactobacillusacidophilus, Enterococcus fecalis) and to assess the therapy influence on quality of life (QQL) in patients with IBS-D. Methods: 158 patients with IBS-D fulfilling Rome II criteria were enrolled the study. Following one week screening, patients were randomly allocated to receive either Medilac-S or Bifico 2 tab. tid for two weeks and then followed up one more week. Symptoms were recorded, including abdominal pain and bloating, frequency of defecation, form of stools, and the sensation of urgency evacuation. QQL was surveyed by questionnaire. Results: 158 patients (101 male and 57 female, mean age 44±12 years) concluded the study. The courses of disease and symtom severity in two groups were comparable at baseline. Each symptom score and total symptoms score were decreased significantly after treatment in both groups (P<0.05). The total effective rate was 41.8% and 49.6% at the end of 1-week and 51.9% and 65.8% at the end of 2-week. The score of QQL reduced from 33.12±23.11 to 18.06±18.73 and 31.88±20.17 to 19.93±17.43, respectively (P<0.01). No No severe adverse events occurred except (3/79) and 4/79) mild adverse events have been recorded but nobody excluded from the study. Conclusion: Our study shows both Medilac-S and Bifico alleviated the systoms of IBS-D and improved the QQL of patients. They will be an effective and safety therapy choice for IBS-D.