Abstract: Objective To observe the clinical effect of probiotics on irritable bowel syndrome (IBS) with small intestinal bacterial overgrowth (SIBO) and provide basis for the application of probiotics in IBS treatment. Methods From January 2012 to August 2013, 100 IBS patients (38 males and 62 females with an average age of 44.7±8.1 years) were chosen as research object in our hospital. According to the result of methane-hydrogen breath test, 64 SIBO patients were divided into 3 groups randomly (antibiotics group, probiotics group and placebo group) and received treatment with rifaximin, Bifidobacterium triple viable capsules and placebo separately. After treatment, the difference of their clinical symptom score, SIBO negative rate and treatment efficiency were compared. Results Compared with the integral before treatment, the clinical symptom integral of antibiotics group (11.39±3.67 vs 4.96±1.19) and probiotics group (11.38±3.46 vs 4.89±1.17) decreased significantly, their difference had statistical significance (P ＜ 0.001). Compared with antibiotics group (4.96±1.19, 86.36%, 72.73%), the clinical symptom integral (4.89±1.17), treatment efficiency (85.71%) and negative rate (71.43%) in probiotics group had no statistical significance (P ＞ 0.05). Compared with placebo group (10.23±3.43, 28.57%, 9.50%), the clinical symptom integral, treatment efficiency and negative rate of antibiotics group and probiotics group had statistical significance (P ＜ 0.05). Conclusion Bifidobacterium triple viable capsules has the same clinical effect with rifaximin. Probiotics can be widely used in the treatment of IBS with SIBO.