Prescribing errors are common, they result in adverse events and harm to patients and it is unclear how best to prevent them because recommendations are more often based on surmized rather than empirically collected data. The aim of this systematic review was to identify all informative published evidence concerning the causes of and factors associated with prescribing errors in specialist and non-specialist hospitals, collate it, analyse it qualitatively and synthesize conclusions from it. Seven electronic databases were searched for articles published between 1985-July 2008. The reference lists of all informative studies were searched for additional citations. To be included, a study had to be of handwritten prescriptions for adult or child inpatients that reported empirically collected data on the causes of or factors associated with errors. Publications in languages other than English and studies that evaluated errors for only one disease, one route of administration or one type of prescribing error were excluded. Seventeen papers reporting 16 studies, selected from 1268 papers identified by the search, were included in the review. Studies from the US and the UK in university-affiliated hospitals predominated (10/16 [62%]). The definition of a prescribing error varied widely and the included studies were highly heterogeneous. Causes were grouped according to Reason's model of accident causation into active failures, error-provoking conditions and latent conditions. The active failure most frequently cited was a mistake due to inadequate knowledge of the drug or the patient. Skills-based slips and memory lapses were also common. Where error-provoking conditions were reported, there was at least one per error. These included lack of training or experience, fatigue, stress, high workload for the prescriber and inadequate communication between healthcare professionals. Latent conditions included reluctance to question senior colleagues and inadequate provision of training. Prescribing errors are often multifactorial, with several active failures and error-provoking conditions often acting together to cause them. In the face of such complexity, solutions addressing a single cause, such as lack of knowledge, are likely to have only limited benefit. Further rigorous study, seeking potential ways of reducing error, needs to be conducted. Multifactorial interventions across many parts of the system are likely to be required.