Indoor residual spraying (IRS) is one of two main malaria vector control strategies with proven public health value1. Unfortunately, rapid spread of insecticide resistance in key vector populations is threatening the success of current tools and the need to develop new products for IRS is a global priority2. Though multiple 3rd Generation IRS (3GIRS) products are now recommended by WHO, their wide-scale uptake is complicated by increased costs and gaps in the evidence base demonstrating their effectiveness. We summarize results from multiple evaluations demonstrating the public health impact of IRS campaigns with 3GIRS products from Mali, Ghana, and Mozambique. Observational analysis of passive malaria case incidence rates in Ségou Region, Mali from 2012 - 2014 showed that IRS with non-pyrethroid insecticides, including 3GIRS3 averted around 300,000 clinical cases of malaria. Suspending IRS operations in Bla district in 2015 was associated with a 70% increase in clinical malaria incidence compared to 2014 rates. During the same time in neighboring Barouéli district, where IRS was consistent in 2014 and 2015, malaria incidence rates remained the same. Preliminary results of a cluster randomized trial4 evaluating the impact of 3GIRS in combination with long-lasting insecticidal nets in Mopeia District, Mozambique show that in 2017, IRS with Actellic® 300CS reduced clinical malaria incidence around 20% (RR of 0.81, CI95 0.79 – 0.83). In Ghana, compared to non-IRS districts in Northern Region, IRS reduced the three month cumulative health facility incidence of clinical malaria by 202 cases per 10,000 person-months in 2015, 311 cases per 10,000 person-months in 2016, and 414 cases per 10,000 person-months in 2017. Evidence from multiple countries demonstrates that IRS with new 3GIRS products is a wise public health investment, especially in areas with documented pyrethroid resistance, where house structures and population densities are appropriate, and even where net coverage is high.