To evaluate the impact of multi-professional teamwork (MPTW) and leadership training interventions on patient outcomes in acute hospital settings. Although investigations of teamwork and leadership training in acute hospital settings indicate that such programs can optimize patient outcomes, evidence-based recommendations on the content, duration and frequency of training programs associated with clinical evidence are still absent. Quantitative systematic review. A search was conducted for relevant papers published during the period from 2000-February 2014. Twelve studies met the inclusion criteria and were appraised for quality and a risk-of-bias assessment was conducted. The review used a structured approach for literature search, data evaluation, analysis and presentation. A narrative summary was used to report results. Two MPTW and leadership interventions in stroke units have the greatest impact on patient outcomes in acute hospital settings. The interventions' impact on patient outcomes, explored in the ten remaining studies, is associated with great uncertainty due to several alternative explanations of the findings. Research designs that test such interventions must be improved before recommendations on the ultimate program can be made. This can be achieved by strengthening the design, methodology and descriptions of interventions and the use of more consistent patient outcomes. Building a safety culture adjacent to implementing teamwork and leadership training interventions is essential for improving patient outcomes.