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Objectives Present a strategy to determine the baseline in endemic areas in the process of vector interruption for Chagas disease (CHD). Methods A social and environmental questionnaire and an entomological survey evaluated the physical conditions of dwellings, the inhabitants' knowledge of CHD, the entomological triatomine indicators and the statistical relationship among these variables. Results Colonization and natural infection with Trypanosoma cruzi exist in Rhodnius prolixus, the principal vector of CHD in Colombia. Colonization was related to palm-thatched houses constructed with adobe or wattle and daub. The Panstrongylus geniculatus vector was found to be colonizing. Almost 50% of the surveyed population associated the term CHD with human disease and 37%, with triatomines. Conclusions R. prolixus can be considered to be the principal vector of T. cruzi in domestic environments and the process of interruption is feasible within the prioritized municipality. New studies are needed to verify the existence of wild populations of R. prolixus that could affect future stages of the process and demonstrate whether P. geniculatus is a factor in the transmission of T. cruzi. These scenarios can be made viable by including the inhabitants throughout the process, since they have been highly sensitive in vector detection inside their houses. The study design presented here can be adapted to other endemic areas of the Region of the Americas.