This study was conducted to evaluate the efficacy and safety of Saccharomyces boulardii strain Unique 28 in patients suffering from acute diarrhoea. A total of 25 patients (average age 30.72±4.38 years) with symptoms of acute diarrhoea (≥3 loose motion in last 24 hours for <7 days) were included upon informed consent and ethical committee approval. All subjects were assigned to consume S. boulardii strain Unique 28 (5×109 cfu/capsule) twice a day for a duration of 10 days. Primary outcome measures such as duration of diarrhoea, frequency of defaecation, abdominal pain and consistency of stool were analysed on day 1, 3, 6 and 10 of the study. Secondary outcome measures were evaluated by assessment of incidence and type of adverse events (blood pressure and pulse rate), physical examination and clinical laboratory tests (complete blood count, glutamic-pyruvic transaminase, serum creatinine, stool examination and microscopy and these tests were performed on day 1 and 10 of the study. The results of the present study indicate that the mean duration of diarrhoea decreased from 34.20±4.25 to 9.40±3.00 (P<0.0001) min per day, frequency of defaecation decreased from 7.04±0.84 to 1.76±0.52 (P<0.0001) times a day, abdominal pain decreased from 3.28±1.06 (severe) to 0.72±0.50 (absent) (P<0.0001) and consistency of stool improved from 3.80±0.50 (watery) to 1.32±0.47 (soft) (P<0.0001). In addition, no significant changes in safety parameters were observed during treatment. Therefore, the present study concludes that S. boulardii strain Unique-28 might be useful in alleviating the symptoms of diarrhoea without any adverse effects.