Objective Syntometrine is an effective uterotonic agent used in preventing primary postpartum haemorrhage but has adverse effects including nausea, vomiting, hypertension and coronary artery spasm. Carbetocin is a newly developed long-acting oxytocin analogue that might be used as an uterotonic agent. We compare the efficacy and safety of intramuscular (IM) carbetocin with IM syntometrine in preventing primary postpartum haemorrhage.Design Prospective, double-blinded, randomised controlled trial.Setting Delivery suite of a university-based obstetrics unit.Population Women with singleton pregnancy achieving vaginal delivery after and throughout 34 weeks.Methods Three hundred and twenty-nine eligible women were randomised to receive either a single dose of 100 microgram IM carbetocin or 1 ml IM syntometrine (a mixture of 5 iu oxytocin and 0.5 mg ergometrine) at the end of second stage of labour.Main outcome measures Difference in haemoglobin drop measured 2 days after delivery between the two groups.Results There was no difference in the drop of haemoglobin concentration within the first 48 hours between the two groups. The incidence of additional oxytocic injections, postpartum haemorrhage (blood loss ‡ 500 ml) and retained placenta were also similar. The use of carbetocin was associated with significant lower incidence of nausea (relative risk [RR] 0.18, 95% confidence interval [CI] 0.04-0.78), vomiting (RR 0.1, 95% CI 0.01-0.74), hypertension 30 minutes (0 versus 8 cases, P < 0.01) and 60 minutes (0 versus 6 cases, P < 0.05) after delivery but a higher incidence of maternal tachycardia (RR 1.68, 95% CI 1.03-3.57).Conclusions IM carbetocin is as effective as IM syntometrine in preventing primary postpartum haemorrhage after vaginal delivery. It is less likely to induce hypertension and has a low incidence of adverse effect. It should be considered as a good alternative to conventional uterotonic agents used in managing the third stage of labour.Keywords Carbetocin, primary postpartum haemorrhage, syntometrine, third stage of labour, uterotonic agents.Please cite this paper as: Leung S, Ng P, Wong W, Cheung T. A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour.