BackgroundProbiotics are effective for treating acute infectious diarrhoea caused by bacteria, but there are inconsistent results for the effectiveness of probiotics for diarrhoea caused by viruses. In this article we want to determine whetherSbsupplementation has an effect on acute inflammatory viral diarrhoea diagnosed with the multiplex panel PCR test. The aim of this study was to evaluate the efficacy ofSaccharomyces boulardii (Sb)as a treatment in patients diagnosed with viral acute diarrhoea.MethodsFrom February 2021 to December 2021, 46 patients with a confirmed diagnosis of viral acute diarrhoea diagnosed with the polymerase chain reaction multiplex assay were enrolled in a double-blind, randomized placebo-controlled trial. Patients received paracetamol 500 mg as a standard analgesic and 200 mg of Trimebutine as an antispasmodic treatment plus 600 mg of Sb (n = 23, 1 × 109/100 mL Colony forming unit) or a placebo (n = 23) orally once daily for eight days. The improvement in and severity of symptoms were measured using a symptom diary, the Patient Global Impression and the Patient Global Impression of Change scales (days 4 and 8), both answered and recorded by the patient.ResultsOf the 46 patients who completed treatment, 24 (52%) were men and 22 (48%) were women. The average age was 35.6 ± 12.28 years (range 18 to 61 years). The average duration of the evolution of illness at the time of diagnosis was 0.85 ± 0.73 days (maximum 2 days). On day 4 after the diagnosis, 20% reported pain and 2% reported fever, but on day 8, no patient reported pain or fever. On day 4, 70% of patients in the Sb group and 26% in the placebo group reported improvement (P = 0.03), based on the Patients’ Global Impression of Change scale, which assesses patient’s rating of overall improvement. These findings suggest that 3 to 4 days of treatment withSbhelped to improve symptoms of diarrhoea caused by a virus.ConclusionTreatment with Sb on acute inflammatory diarrhoea of viral aetiology shows no changes regarding the severity of the symptoms; nevertheless, it seems to impact improvement positively.Trial registration22CEI00320171130 dated on 16/12/2020, NCT05226052 dated on 07/02/2022.