Background: Irritable bowel syndrome (IBS) is a gastrointestinal syndrome characterized by chronic pain and irregular bowel movement in the absence of organic causes. IBS may be predominant in diarrhea or constipation. One of the pathophysiological factors believed to cause the prevalence of diarrhea in IBS (IBS-D) is a high level of serotonin, especially after meals. There are two types of serotonin that involve the gastrointestinal system, type 3 (HT3) and type 4 (HT4). The purpose of this study is to evaluate the efficacy of ondansetron, which is a selective 5-HT3 receptor antagonist used as an antiemitting agent, in the treatment of IBS-D. Literature search strategy: A literature search was conducted in Pubmed using the following MeSH terms: ondansetron, IBS, treatment. Pharmacological terms were combined with the remaining terms with the Boolean operator “and”. This was then limited to the English language, for the last five years and human. A total of 2 articles were identified. Of these, 1 met the following criteria: randomized control trial and evaluated the effectiveness of using ondansetron in the treatment of IBS-D. The other article was excluded because it was not relevant to the question. Literature Review: A Randomized Trial of Ondansetron for the Treatment of Irritable Bowel Syndrome with Diarrhea was a two-center, double-blind, placebo-controlled crossover study of ondansetron 4 mg. /tablet compared to placebo. Study inclusion criteria were age 18 to 75 years, IBS-D patients meeting Rome III criteria, women of childbearing age who had to agree to use contraceptives during the study, no evidence of inflammatory bowel disease/colitis microscopic and capable of providing consensus information. Exclusion criteria were pregnancy or br...... middle of paper ......gency score was significantly lower in ondansetron compared to placebo -0.32 (-0.45 to -0.18 ) <0.001, but there was no statistical significance difference between ondansetron and placebo -0.13 (-0.27 to 0.01) P = 0.070. The PPA showed the same results as the ITT. The only frequent side effect was constipation, which occurred in 9% of ondansetron patients and 2% of the placebo group. Other less frequent side effects, which included headache, rectal bleeding, back pain and abdominal pain, were almost the same between the two groups. Conclusions: Ondansetron showed clinical efficacy in modifying stool shape and decreasing the urgency of deification, but no improvement in term. of pain. Furthermore, it showed a well-tolerated side effect that could be reduced by reducing the dose. So, for IBS-D patients who complain of stool urgency, ondansetron will be an excellent treatment option for them.