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Objective: The aim was to analyze the spatial association and relative risk (RR) of leprosy cases diagnosed in southern Brazil and in the Argentinean province of Misiones during 2010 to 2016. Methods: This ecological-type epidemiological study analyzed data from the Health Ministries of both countries. The analysis included frequency measures, spatial autocorrelation, RR cluster analysis and map construction. Results: A hyperendemic occurrence was identified in all study regions, in the state of Paraná 71.2% of the municipalities were hyperendemic and in Misiones, Argentina 41.2%. The GI* statistical analysis showed clusters of high incidence rates in the state of Paraná and low-risk clusters in much of the state of Rio Grande do Sul, both in Brazil. The analysis indicated an area with RR equal to 3.87 - (p <.0001) when considering the entire territory and an RR of 2.80 - (p <.0001) excluding the state of Paraná, with the number of departments of Misiones, Argentina included in the risk clusters increasing significantly. Conclusions: The findings indicate a high probability of similar illness in adjacent areas, according to their relative position in space, as the occurrence of the disease is influenced by neighboring clusters. [ABSTRACT FROM AUTHOR]