Author summary The results demonstrate the ecological potential ofTriatoma brasiliensisin the northeastern caatinga and how this species uses the resources available in nature or in the modified environment by man. Triatomines were collected in peridomestic, sylvatic, and intradomicile habitats. House infestations were evaluated on five occasions, with spraying of infested houses.T.brasiliensiswas responsible for the high rates of dispersal, infestation, colonization andTrypanosoma cruziinfection in all catches and environments studied here. Spraying strongly reduced the infestation, but the number of triatomines rapidly returned to previous levels. Peridomicile represents a complex set of overlapping infested sites forming a network of shelters that favor the establishment and proliferation of triatomine colonies. Molecular characterization ofT.cruziisolated from triatomines and identification of their food sources emphasize the overlap of habitats and interaction among triatomines, synanthropic reservoirs and humans, increasing the risk of parasite transmission. Therefore, it is clear the need for maintenance of vector control fully and systematically with the use of appropriate strategies where interventions should consider regional ecoepidemiologic differences and the influence of environmental, socioeconomic and cultural factors inT.cruzytransmission process into domicile environment. The northeastern semiarid region stands out in the Brazilian context regarding the eco-epidemiology of Chagas disease, in whichTriatoma brasiliensisis the main vector ofTrypanosoma cruzi. Persistent house invasion threatens the relative levels of progress achieved over previous decades. We conducted an intervention trial with a five-year follow-up to assess the impacts of residual spraying with pyrethroid insecticides on house infestation withT.brasiliensisin 18 rural villages (242 houses) located in the Taua, Ceara. House infestations were assessed by systematic manual searches for triatomines in every domestic and peridomestic habitat on five occasions. Triatomines were collected in peridomestic (57.5%), sylvatic (35.8%), and intradomiciliary (6.7%) habitats. The most important ecotopes ofT.brasiliensiswere containing roofing tiles, bricks or rocks (23.4% +/- 9.1). Residual insecticide spraying substantially reduced baseline house infestation rates from 27.9% to 5.9% by 6 months post first spraying (MPS). The decline was substantially greater in intradomiciles (11.2% to 0.8%) than in peridomiciles (16.7% to 5%). The mean relative density of triatomines recovered its preintervention values at 14 MPS in intradomiciles, and in the main peridomestic ecotopes. The house infestation levels recorded at 14 MPS persisted thereafter despite all reinfested houses were selectively sprayed on every occasion. Overall average bug infection rates withT.cruziin the five occasions were in intradomiciles (11.1%), peridomiciles (4.7%) and wild habitats (3.3%). In peridomicileT.cruziinfection rates decreased significantly at all stages after chemical intervention. In intradomicile, the only significant difference occurred at 20 MPS (7.7% to 30.8%). The vectorial capacity ofT.brasiliensis, combined with its invasive potential from sylvatic sources and the limited effectiveness of chemical control in the harshcaatingalandscape, pose serious obstacles to the definite elimination of domestic transmission risks. Systematic vector surveillance supported by community participation and locally adapted environmental management measures are needed to reduce the risks of establishment of domestic transmission withT.cruziin this region.