Background: Larvicides are typically applied to fxed and fndable mosquito breeding sites, such as fsh farming ponds used in commercial aquaculture, to kill immature forms and thereby reduce the size of adult malaria vector populations. However, there is little evidence suggesting that larviciding may suppress community-wide malaria transmission outside Africa. Here, we tested whether the biological larvicide VectoMax FG applied at monthly intervals to fsh farming ponds can reduce malaria incidence in Amazonian Brazil. Methods: This study was carried out in Vila Assis Brasil (VAB; population 1700), a peri-urban malaria hotspot in northwestern Brazil with a baseline annual parasite incidence of 553 malaria cases per 1000 inhabitants. The interven‑ tion consisted of monthly treatments with 20 kg/ha of VectoMax FG of all water-flled fsh ponds in VAB (n ranging between 167 and 170) with a surface area between 20 and 8000 m2 , using knapsack power mistblowers. We used single-group interrupted time-series analysis to compare monthly larval density measurements in fsh ponds during a 14-month pre-intervention period (September 2017–October 2018), with measurements made during November 2018–October 2019 and shortly after the 12-month intervention (November 2019). We used interrupted time-series analysis with a comparison group to contrast the malaria incidence trends in VAB and nearby nonintervention locali‑ ties before and during the intervention. Results: Average larval densities decreased tenfold in treated fsh farming ponds, from 0.467 (95% confdence interval [CI], 0.444–0.490) anopheline larvae per dip pre-intervention (September 2017–October 2018) to 0.046 (95% CI, 0.041–0.051) larvae per dip during (November 2018–October 2019) and shortly after the intervention (Novem‑ ber 2019). Average malaria incidence rates decreased by 0.08 (95% CI, 0.04–0.11) cases per 100 person-months (P<0.0001) during the intervention in VAB and remained nearly unchanged in comparison localities. We estimate that the intervention averted 24.5 (95% CI, 6.2–42.8) malaria cases in VAB between January and December 2019. Conclusions: Regular larviciding is associated with a dramatic decrease in larval density and a modest but signifcant decrease in community-wide malaria incidence. Larviciding may provide a valuable complementary vector control strategy in commercial aquaculture settings across the Amazon.