To determine the effect of working 12 h or more on a single shift in an acute care hospital setting compared with working less than 12 h on rates of error among nurses. Systematic review. A three-step search strategy was utilised. An initial search of Cochrane, the Joanna Briggs Institute (JBI), MEDLINE and CINAHL was undertaken. A second search using all identified keywords and index terms was then undertaken across all included databases (Embase, Current contents, Proquest Nursing and Allied Health Source, Proquest Theses and Dissertations, Dissertation Abstracts International). Thirdly, reference lists of identified reports and articles were searched for additional studies. Studies published in English before August 2014 were included. Following review of title and abstract of 5429 publications, 26 studies were identified as meeting the inclusion criteria and selected for full retrieval and assessment for methodological quality. Of these, 13 were of sufficient quality to be included for review. Six studies reported higher rates of error for nurses working greater than 12 h on a single shift, four reported higher rates of error on shifts of up to 8 h, and three reported no difference. The six studies reporting significant rises in error rates among nurses working 12 h or more on a single shift comprised 89% of the total sample size (N=60,780 with the total sample size N=67,967). The risk of making an error appears higher among nurses working 12 h or longer on a single shift in acute care hospitals. Hospitals and units currently operating 12 h shift systems should review this scheduling practice due to the potential negative impact on patient outcomes. Further research is required to consider factors that may mitigate the risk of error where 12 h shifts are scheduled and this cannot be changed.