BACKGROUND: Offender health is deemed a priority issue by the Department of Health. Peer support is an established feature of prison life in England and Wales; however, more needs to be known about the effectiveness of peer-based interventions to maintain and improve health in prison settings. OBJECTIVES: The study aimed to synthesise the evidence on peer-based interventions in prison settings by carrying out a systematic review and holding an expert symposium. Review questions were (1) what are the effects of peer-based interventions on prisoner health and the determinants of prisoner health?, (2) what are the positive and negative impacts on health services within prison settings of delivering peer-based interventions?, (3) how do the effects of peer-based approaches compare with those of professionally led approaches? and (4) what are the costs and cost-effectiveness of peer-based interventions in prison settings? DATA SOURCES: For the systematic review, 20 electronic databases including MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature and EMBASE were searched from 1985. Grey literature and relevant websites were also searched. To supplement the review findings 58 delegates, representing a variety of organisations, attended an expert symposium, which provided contextual information. REVIEW METHODS: Two reviewers independently selected studies using the following inclusion criteria: population – prisoners resident in prisons and young offender institutions; intervention – peer-based interventions; comparators: review questions 3 and 4 compared peer-led and professionally led approaches; outcomes – prisoner health or determinants of health, organisational/process outcomes or views of prison populations; study design: quantitative, qualitative and mixed-methods evaluations. Two reviewers extracted data and assessed validity using piloted electronic forms and validity assessment criteria based on published checklists. Results from quantitative studies were combined using narrative summary and meta-analysis when appropriate; results from qualitative studies were combined using thematic synthesis. RESULTS: A total of 15,320 potentially relevant papers were identified of which 57 studies were included in the effectiveness review and one study was included in the cost-effectiveness review; most were of poor methodological quality. A typology of peer-based interventions was developed. Evidence suggested that peer education interventions are effective at reducing risky behaviours and that peer support services provide an acceptable source of help within the prison environment and have a positive effect on recipients; the strongest evidence came from the Listener scheme. Consistent evidence from many predominantly qualitative studies suggested that being a peer deliverer was associated with positive effects across all intervention types. There was limited evidence about recruitment of peer deliverers. Recurring themes were the importance of prison managerial and staff support for schemes to operate successfully, and risk management. There was little evidence on the cost-effectiveness of peer-based interventions. An economic model, developed from the results of the effectiveness review, although based on data of variable quality and a number of assumptions, showed the cost-effectiveness of peer-led over professionally led education in prison for the prevention of human immunodeficiency virus (HIV) infection. LIMITATIONS: The 58 included studies were, on the whole, of poor methodological quality. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health. Peer support services can also provide an acceptable source of help within the prison environment and can have a positive effect on recipients. This was confirmed by expert evidence. Research into cost-effectiveness is sparse but a limited HIV-specific economic model, although based on a number of assumptions and evidence of variable quality, showed that peer interventions were cost-effective compared with professionally led interventions. Well-designed intervention studies are needed to provide robust evidence including assessing outcomes for the target population, economic analysis of cost-effectiveness and impacts on prison health services. More research is needed to examine issues of reach, utilisation and acceptability from the perspective of recipients and those who choose not to receive peer support. STUDY REGISTRATION: This study was registered as PROSPERO CRD42012002349. FUNDING: The National Institute for Health Research Health Services and Delivery Research programme.