Background <p>Residual spraying with pyrethroid insecticides remains the main tool in the control of vector-borne transmission of Chagas disease. However, its efficacy has been compromised in regions with pyrethroid-resistant populations of triatomines, as in the Gran Chaco region, where <i>Triatoma infestans</i> has developed high levels of resistance. To cope with it, xenointoxication has emerged as a promising strategy. As part of a cluster-randomized trial aimed at evaluating the effects of treating dogs with fluralaner on (peri)domestic infestation and <i>T. cruzi</i> infection, we evaluated the effect of fluralaner administration to dogs on the feeding profile of <i>T. infestans</i> with particular emphasis on variations in feeding indices on humans, dogs, and chickens.</p> Methods <p>We identified bloodmeal sources by enzyme-linked immunosorbent assays on a sample of the <i>T. infestans</i> collected before (February 2020) and after (December 2020) the oral administration of fluralaner to dogs in treated clusters. We analyzed 327 triatomines collected pre-intervention and 210 triatomines post-intervention. Peridomestic ecotopes were stratified as of high (HRP) and low risk (LRP) of <i>T. cruzi</i> transmission. HRP mainly encompassed kitchens, storerooms, and granaries and the LRP, ecotopes associated with poultry. Only triatomines collected in domiciles and HRP were included for analyses.</p> Results <p>In domiciles, humans were the primary bloodmeal source regardless of the intervention arm or time point (&gt; 72%). In HRP, bloodmeals on chickens predominated (&gt; 78%), while dogs (range 0–18%), humans (0–7%), and rodents (1–7%) acted as secondary or marginal sources. No significant effect of treatment arm, intervention time point, and their interaction on the occurrence of bloodmeals on humans, dogs, or chickens was detected via logistic regressions conducted separately for domiciles and HRP. Conversely, dog bloodmeals decreased post-intervention in the treated arm.</p> Conclusions <p>Based on these and previously reported results we conclude that we have no evidence to support that the administration of fluralaner to domestic dogs diverts the feeding profile of <i>T. infestans</i> to humans at 10&#xa0;months post-intervention. These findings further support the use of fluralaner in xenointoxication to manage pyrethroid-resistant triatomine populations.</p> Graphical Abstract <p></p>