Gastrointestinal symptoms are the most common side-effects of tegaserod therapy. In data pooled from Phase III randomized controlled trials in patients with irritable bowel syndrome with constipation, diarrhoea was reported by 8.8% of patients treated with tegaserod 6 mg b.d. vs. 3.8% of patients treated with placebo. Similar rates were observed in international post-US marketing randomized controlled trials. In most patients, tegaserod-induced diarrhoea was mild and transient. In randomized controlled trials, it did not elicit fluid or electrolyte disturbances, and fewer than 3% of irritable bowel syndrome patients discontinued tegaserod due to diarrhoea. The incidence of other gastrointestinal symptoms (e.g. abdominal pain, nausea and flatulence) was similar in tegaserod-treated and placebo-treated patients. Pooled analysis of Phase III and post-US marketing randomized controlled trials did not demonstrate significant differences between tegaserod-treated and placebo-treated patients in the incidence of abdominal/pelvic surgery. No episodes of ischaemic colitis were reported in tegaserod-using patients in any Phase III or post-marketing randomized controlled trials, and post-marketing surveillance indicated that the rate of ischaemic colitis in tegaserod-using patients was lower than that in non-tegaserod-using patients. Pooled analysis of Phase III randomized controlled trials demonstrated an increase in the incidence of headaches in tegaserod-treated (6 mg b.d.) vs. placebo-treated patients (15% vs. 12.3%, respectively; P < 0.05), although post-US marketing randomized controlled trials did not demonstrate this increase. Other extra-gastrointestinal adverse events occurred with similar frequency in tegaserod-treated and placebo-treated patients. Tegaserod-treated patients in randomized controlled trials did not demonstrate significant prolongation of the QTc interval or cardiac arrhythmias compared with placebo-treated patients. In summary, tegaserod exhibits a favourable safety and tolerability profile in irritable bowel syndrome patients based on data from clinical trials.