Dengue has become the most important viral disease of humans transmitted by arthropods in tropical and subtropical urban regions. Most countries have not been able to maintain permanent larval mosquito control programs against Aedes aegypti, the main vector of dengue and yellow fever, partly because of misguided reliance on using insecticidal space sprays to kill adult mosquitoes. Control actions targeting larvae are based on regular treatment with insecticides of every mosquito developmental site, usually artificial containers found inside or around human dwellings. The reasons why sustained larval control programs cannot reduce infestations to the desired levels have rarely been investigated. A five-year intervention program conducted in Clorinda, northeastern Argentina, reduced significantly larval infestations compared to pre-intervention levels. Infestations depended on weather variations, pre-intervention larval infestation, and the percentage of houses that were visited and treated with larvicides. Although the program did not reach the low levels of infestation desired, it most likely prevented or limited new local dengue outbreaks. Large containers for permanent water storage were the most important mosquito development site. For further improvements, a multifaceted intervention program is needed. It should include intensified surveillance and treatment coverage with larvicides that last longer, more efforts on reducing the potential number of mosquito development sites, and a broad social participation aiming at long-term sustainability.