Irritable bowel syndrome (IBS) is one of the most common diagnoses in gastroenterology, but current therapies are inefficient. Recent clinical trials suggest beneficial effects of certain probiotics in IBS. Because of the heterogeneity of IBS a probiotic combination may be more efficient than a single strain. We screened for optimal strains, and developed a multispecies probiotic combination consisting of L. rhamnosus GG, L. rhamnosus Lc705, P. freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99. The clinical efficacy of the probiotic combination was evaluated in IBS patients in a randomised, double-blind, placebo-controlled six-month intervention. During six months the subjects received daily either probiotic supplementation or placebo. IBS symptoms were followed by symptom diaries. The probiotic supplementation demonstrated significant value in reducing IBS symptoms. At the end of the study period the total symptom score (abdominal pain + distension + flatulence + rumbling) had reduced with 42% in probiotic group versus 6% for instance anti-inflammatory effects, balancing of the microbiota or motility-related effects induced by the probiotic. The probiotic activity may be enhanced by synergistic effects of the combination that each strain alone would not hold. In conclusion, we found a probiotic combination of LGG and three other strains to be effective in alleviating IBS symptoms.