BACKGROUND Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms have included pharmacological, behavioural and complementary therapies. Although scopolamine (hyoscine) has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness. OBJECTIVE To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology. METHODS The Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2007), MEDLINE (OVID, 1966 to May 2007), EMBASE (1974 to May 2007) CINAHL (OVID, 1982 to May 2007) and reference lists of retrieved studies were searched for relevant studies. No language restrictions were applied. The date of the last search was May 2007. METHODS All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination were included. Outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects were considered. METHODS Data from the studies were extracted independently by two authors using standardised forms. Study quality was assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was calculated using the random-effects model. RESULTS Of 35 studies considered potentially relevant, 14 studies enrolling 1025 subjects met the entry criteria. Scopolamine was administered via transdermal patches, tablets or capsules, oral solutions or intravenously. Scopolamine was compared against placebo, calcium channel antagonists, antihistamine, methscopolamine or a combination of scopolamine and ephedrine. Studies were generally small in size and of varying quality. Scopolamine was more effective than placebo in the prevention of symptoms. Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior (versus methscopolamine) or equivalent (versus antihistamines) as a preventative agent. Evidence comparing scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal. Although sample sizes were small, scopolamine was no more likely to induce drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth was more likely with scopolamine than with methscopolamine or cinnarizine. No studies were available relating to the therapeutic effectiveness of scopolamine in the management of established symptoms of motion sickness. CONCLUSIONS The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, no randomised controlled trials were identified that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.