Stigma is a common phenomenon worldwide and infectious diseases like HIV/AIDS and leprosy are often associated with high levels of stigma. Several studies have been conducted concerning the effects of stigma and the impact on social participation, but comparative studies are rare. The objective of this study was to identify differences and similarities between HIV/AIDS and leprosy-related stigma. From April till July 2009, 190 questionnaire-based interviews were conducted to assess the levels of internalized stigma (Internalized Stigma of Mental Illness scale), perceived stigma (Explanatory Model Interview Catalogue stigma scale) and social participation (Participation scale) in a cross-sectional sample of people affected by leprosy (PL) and people living with HIV/AIDS (PLHA). Respondents were selected from several hospitals, charity projects and during home visits in Vellore district, Tamil Nadu. Our results showed that both PLHA (n=95) and leprosy-affected respondents (n=95) faced a substantial burden of internalized and perceived stigma, with the former reporting a significantly higher level of stigma. As a result, PLHA faced more frequent and also more severe participation restrictions than PL. Especially, restrictions in work-related areas were reported by the majority of the respondents. In conclusion, PLHA faced a significantly higher level of stigma and participation restriction than PL. However, the latter also reported a substantial burden of stigma and participation restrictions. The study suggests that it may be possible to develop joint interventions based on the commonalities found. More research is needed to define these more precisely and to test the effectiveness of such joint interventions in reducing stigma and improving social participation. Copyright © 2011 Taylor and Francis Group, LLC.