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Traditional methods of vector control have proven insufficient to reduce the alarming incidence of dengue, Zika, and chikungunya in endemic countries. The bacterium symbiont Wolbachia has emerged as an efficient pathogen-blocking and self-dispersing agent that reduces the vectorial potential of Aedes aegypti populations and potentially impairs arboviral disease transmission. In this work, we report the results of a large-scale Wolbachia intervention in Ilha do Governador, Rio de Janeiro, Brazil. w Mel-infected adults were released across residential areas between August 2017 and March 2020. Over 131 weeks, including release and post-release phases, we monitored the w Mel prevalence in field specimens and analyzed introgression profiles of two assigned intervention areas, RJ1 and RJ2. Our results revealed that w Mel successfully invaded both areas, reaching overall infection rates of 50-70% in RJ1 and 30-60% in RJ2 by the end of the monitoring period. At the neighborhood-level, w Mel introgression was heterogeneous in both RJ1 and RJ2, with some profiles sustaining a consistent increase in infection rates and others failing to elicit the same. Correlation analysis revealed a weak overall association between RJ1 and RJ2 ( r = 0.2849, p = 0.0236), and an association at a higher degree when comparing different deployment strategies, vehicle or backpack-assisted, within RJ1 ( r = 0.4676, p < 0.0001) or RJ2 ( r = 0.6263, p < 0.0001). The frequency knockdown resistance ( kdr ) alleles in w Mel-infected specimens from both areas were consistently high over this study. Altogether, these findings corroborate that w Mel can be successfully deployed at large-scale as part of vector control intervention strategies and provide the basis for imminent disease impact studies in Southeastern Brazil., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gesto, Pinto, Dias, Peixoto, Costa, Kutcher, Montgomery, Green, Anders, Ryan, Simmons, O’Neill and Moreira.)