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Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of\n                      <jats:italic>w<\/jats:italic>\n                      Mel-infected\n                      <jats:italic>Ae<\/jats:italic>\n                      .\n                      <jats:italic>aegypti<\/jats:italic>\n                      . We report the public health outcomes from phased, large-scale releases of\n                      <jats:italic>w<\/jats:italic>\n                      Mel-\n                      <jats:italic>Ae<\/jats:italic>\n                      .\n                      <jats:italic>aegypti<\/jats:italic>\n                      mosquitoes throughout three contiguous cities in the Aburr\u00e1 Valley, Colombia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>\n                      Following pilot releases in 2015\u20132016, staged city-wide\n                      <jats:italic>w<\/jats:italic>\n                      Mel-\n                      <jats:italic>Ae<\/jats:italic>\n                      .\n                      <jats:italic>aegypti<\/jats:italic>\n                      deployments were undertaken in the cities of Bello, Medell\u00edn and Itag\u00fc\u00ed (3.3 million people) between October 2016 and April 2022. The impact of the\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medell\u00edn and 97% in Itag\u00fc\u00ed, following establishment of\n                      <jats:italic>w<\/jats:italic>\n                      Mel at \u226560% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburr\u00e1 Valley following\n                      <jats:italic>w<\/jats:italic>\n                      Mel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD\/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in\n                      <jats:italic>w<\/jats:italic>\n                      Mel-treated versus untreated neighbourhoods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/Significance<\/jats:title>\n                    <jats:p>\n                      Stable introduction of\n                      <jats:italic>w<\/jats:italic>\n                      Mel into local\n                      <jats:italic>Ae<\/jats:italic>\n                      .\n                      <jats:italic>aegypti<\/jats:italic>\n                      populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous\n                      <jats:italic>Wolbachia<\/jats:italic>\n                      releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03631719\" xlink:type=\"simple\">NCT03631719<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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