Background Agitation and aggression are significant problems in acute psychiatric units. There is little consensus on which drug is most effective and safest for sedation of these patients. Aims To compare the effectiveness and safety of haloperidol v. droperidol for patients with agitation and aggression. Method In a masked, randomised controlled trial (ACTRN12611000565943) intramuscular droperidol (10 mg) was compared with intramuscular haloperidol (10 mg) for adult patients with acute behavioural disturbance in a psychiatric intensive care unit. The primary outcome was time to sedation within 120 min. Secondary outcomes were use of additional sedation, adverse events and staff injuries. Results From 584 patients, 110 were randomised to haloperidol and 118 to droperidol. Effective sedation occurred in 210 (92%) patients within 120 min. There was no significant difference in median time to sedation: 20 min (interquartile range 15-30, range 10-75) for haloperidol v. 25 min (IQR 15-30, range 10-115) for droperidol (P = 0.89). Additional sedation was used more often with haloperidol (13% v. 5%, P = 0.06), but adverse effects were less common with haloperidol (1% v. 5%, P = 0.12). There were 8 staff injuries. Conclusions Both haloperidol and droperidol were effective for sedation of patients with acute behavioural disturbance.