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<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.