Background: Underlying systems factors have been seen to be crucial contributors to the occurrence of medication errors. By understanding the causes of these errors, the most appropriate interventions can be designed and implemented to minimise their occurrence. Objective: This study aimed to systematically review and appraise empirical evidence relating to the causes of medication administration errors (MAEs) in hospital settings. Data Sources: Nine electronic databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, ASSIA, PsycINFO, British Nursing Index, CINAHL, Health Management Information Consortium and Social Science Citations Index) were searched between 1985 and May 2013. Study Selection: Inclusion and exclusion criteria were applied to identify eligible publications through title analysis followed by abstract and then full text examination. English language publications reporting empirical data on causes of MAEs were included. Reference lists of included articles and relevant review papers were hand searched for additional studies. Studies were excluded if they did not report data on specific MAEs, used accounts from individuals not directly involved in the MAE concerned or were presented as conference abstracts with insufficient detail. Data Appraisal and Synthesis Methods: A total of 54 unique studies were included. Causes of MAEs were categorised according to Reason's model of accident causation. Studies were assessed to determine relevance to the research question and how likely the results were to reflect the potential underlying causes of MAEs based on the method(s) used. Results: Slips and lapses were the most commonly reported unsafe acts, followed by knowledge-based mistakes and deliberate violations. Error-provoking conditions influencing administration errors included inadequate written communication (prescriptions, documentation, transcription), problems with medicines supply and storage (pharmacy dispensing errors and ward stock management), high perceived workload, problems with ward-based equipment (access, functionality), patient factors (availability, acuity), staff health status (fatigue, stress) and interruptions/distractions during drug administration. Few studies sought to determine the causes of intravenous MAEs. A number of latent pathway conditions were less well explored, including local working culture and high-level managerial decisions. Causes were often described superficially; this may be related to the use of quantitative surveys and observation methods in many studies, limited use of established error causation frameworks to analyse data and a predominant focus on issues other than the causes of MAEs among studies. Limitations: As only English language publications were included, some relevant studies may have been missed. Conclusions: Limited evidence from studies included in this systematic review suggests that MAEs are influenced by multiple systems factors, but if and how these arise and interconnect to lead to errors remains to be fully determined. Further research with a theoretical focus is needed to investigate the MAE causation pathway, with an emphasis on ensuring interventions designed to minimise MAEs target recognised underlying causes of errors to maximise their impact. © 2013 The Author(s).