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Individuals in contact with patients who have leprosy have an increased risk of disease exposure, which reinforces the need for chemoprophylactic measures, such as the use of rifampicin.The objective of the review was to synthesize the best available evidence regarding the effectiveness of rifampicin chemoprophylaxis for contacts with patients with leprosy, and to synthesize the best available evidence on the experience and acceptability of rifampicin chemoprophylaxis as reported by the contacts and health professionals involved in the treatment of leprosy or Hansen's disease.In the quantitative component, individuals in contact with leprosy patients were included. In the qualitative component, in addition to contacts, health professionals who were in the practice of treating leprosy were included.The quantitative component considered as an intervention rifampicin at any dose, frequency and mode of administration, and rifampicin combination regimens.The qualitative component considered as phenomena of interest the experience and acceptability of rifampicin chemoprophylaxis.The quantitative component considered experimental and observational studies whereas the qualitative component considered studies that focused on qualitative data, including but not limited to, designs such as phenomenology, grounded theory, ethnography and action-research.The quantitative component considered studies that reported on outcomes such as the development of clinical leprosy in the contacts of patients who had leprosy, incidence rates, adverse effects and safety/harmful effects of the intervention.A three-step strategy for published and unpublished literature was used. The search for published studies included: PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Scopus, Web of Science, National Institute for Health and Clinical Excellence, Latin American and Caribbean Health Sciences Literature; and Google Scholar and EVIPnet for unpublished studies. Studies published from the time of the respective database inception to January 2016 in English, Spanish, Portuguese, Japanese and Chinese were considered.Two reviewers independently assessed the studies for methodological quality using standardized critical appraisal instruments from the Joanna Briggs Institute.Standardized data extraction tools developed by the Joanna Briggs Institute were used to extract quantitative and qualitative data from papers included in the review.Due to clinical and methodological heterogeneity in the interventions of the included studies, no statistical meta-analysis was possible. Quantitative and qualitative research findings are presented in narrative form.Following critical appraisal, eight studies were included in this review, seven quantitative and one qualitative. The reduction in incidence of leprosy, using one dose of rifampicin in the first two years, was 56.5%; in the follow up period of one to four years, the reduction was 34.9%. The combination of rifampicin and the Bacillus Calmette-Guérin vaccine showed a preventative effect of 80% against the disease. The only controlled clinical trial using two doses of rifampicin was community-based and did not indicate effectiveness of the intervention. The qualitative findings showed social acceptability of rifampicin.Chemoprophylaxis with one dose of rifampicin is found to be effective in preventing contacts of leprosy patients from contracting the disease. Also, there is indication that this strategy is socially accepted.