Abstract The role of 5-hydroxytryptamine 3 (HT 3) antagonists in the treatment of delayed emesis is still controversial. To evaluate whether 5-HT 3 antagonists can add to the efficacy of corticosteroids in controlling delayed emesis, we performed a randomised, prospective, open study comparing ondansetron plus dexamethasone with dexamethasone alone in cisplatin-treated patients. 149 cisplatin-naı̈ve patients with lung cancer received at least 60 mg/m 2 of cisplatin and were treated with dexamethasone 32 mg intravenously (i.v.) and granisetron 3 mg i.v. on day 1. Patients were randomly assigned to receive either dexamethasone 16 mg i.v. alone (arm A) or dexamethasone plus ondansetron 8 mg daily (arm B) on days 2–4. None of the efficacy variables related to control of delayed emesis differed significantly between the two arms. In conclusion, there does not appear to be sufficient evidence to support the prolonged use of 5-HT 3 receptor antagonists after 24 h of cisplatin-containing chemotherapy.