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These treatments vary in administration frequency (eg, daily; short\u2010course therapy) and target various pathophysiologic factors. Safety profiles vary considerably by treatment among <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D therapies. The number needed to harm (defined as the number of patients treated to encounter an adverse event) was lowest (worse) for antidepressants (8.5) and highest (best) for probiotics (35), and the number needed to harm (defined as the number of patients who discontinued due to an adverse event) was lowest for tricyclic antidepressants (9) and highest for rifaximin (8971). Notable safety concerns with <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D treatments include pancreatitis with eluxadoline, ischaemic colitis and serious complications of constipation with alosetron, and cardiac adverse events with loperamide and tricyclic antidepressants. Treatment decisions need to account for medication risks and adverse events for each patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Multiple treatment options are now available for patients with <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010D. However, the safety profiles of these agents vary widely by number needed to harm value. 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