BACKGROUND: Probiotics are a promising solution for managing irritable bowel syndrome (IBS). () I-3856 has already demonstrated beneficial effects in IBS subjects, particularly in IBS with predominant constipation (IBS-C). AIM: To confirm the efficacy of I-3856 in the management of gastrointestinal symptoms in IBS-C. METHODS: A randomized, double-blind, placebo-controlled clinical study was performed in a total of 456 subjects. After a run-in period, subjects were randomly assigned to the group receiving I-3856 (8 × 10 CFU daily) or the placebo for 8 wk, and they performed daily self-evaluations of gastrointestinal symptoms. The primary objective was to assess the effect of the probiotic on abdominal pain. The secondary objectives were the evaluation of other gastrointestinal symptoms, bowel movement frequency and consistency, and quality of life (QOL). RESULTS: A significantly higher proportion of abdominal pain responders was reported in the Probiotic group (45.1% 33.9%, = 0.017). A nonsignificant difference in the area under the curve for abdominal pain over the second month of supplementation was observed in subjects receiving probiotic placebo [ = 0.073, 95%CI: -0.59 (-1.23; 0.05)]. No statistically significant differences were reported in the evolution of bowel movement frequency and stool consistency between the groups. After 8 wk of supplementation, the overall QOL score was significantly higher in the Probiotic group than in the Placebo group [ = 0.047, 95%CI: 3.86 (0.52; 7.20)]. Furthermore, exploratory analyses showed statistically significant and clinically relevant improvements in QOL scores in abdominal pain responders nonresponders. CONCLUSION: The results of this clinical study confirmed the abdominal pain alleviation properties of I-3856 in IBS-C. Abdominal pain relief was associated with improved QOL. ClinicalTrials.gov identifier: NCT03150212.