In a randomized, double-blind trial, we compared i.v. ondansetron 4 mg (control), i.v. ondansetron 4 mg and cyclizine 50 mg (combination) and i.v. saline 0.9% (placebo), given after induction of standardized anaesthesia, for the prevention of nausea and vomiting (PONV) after day-case gynaecological laparoscopic surgery. Compared with placebo, fewer patients in the control group vomited (9/20 versus 11/59, P=0.02) or needed rescue antiemetic (7/20 versus 9/59, P=0.06) before discharge. Compared with the control, fewer patients in the combination group (n=60) vomited (11/59 versus 2/60, P=0.01) or needed rescue antiemetic (29/59 versus 2/60, P=0.03) before discharge. The incidence of vomiting in the combination group was less than 5% overall. Compared with the control, the combination group had a significantly lower incidence (P=0.001) and severity (P<0.00) of nausea after discharge and more patients with no PONV at any time during the study (15/59 versus 27/60, P=0.03). Unlike the placebo and control groups, no patient receiving combination prophylaxis was admitted overnight for PONV management.