Among the few mosquito larvicides available in the market, Bacillus thuringiensis subsp. israelensis (Bti) and B. sphaericus (Bs) represent the most environmentally safe alternatives. The combination of the 2 products is known to overcome their specific limitations by producing a synergistic effect. The aim of the study was to assess the effect and persistence of a single treatment with a granular Bti + Bs formulation on highly vegetated ditches in northeastern Italy that represents the primary rural larval sites for Culex pipiens, the primary vector of the West Nile virus in Europe. The analysis takes into account the nonlinear temporal effects on the population dynamics of larvae and pupae. The results showed a dramatic reduction in mosquito larval abundance 24 h posttreatment (93%) and was effective against larvae up to 22 days (100%). The residual effect after 28 days was 99.5%, and a limited residual effect was observed after 39 days (31.2%). A reduction in pupal density was observed after 4 days (70%) and was >98% from days 14 to 28 posttreatment, persisting for up to 39 days (84% after 39 days). The results demonstrate the effective use of the Bti + Bs formulation against Cx. pipiens in vegetated ditches in rural areas. Our modeling framework provides a flexible statistical approach to predict the residual effect of the product over time, in order to plan a seasonal intervention scheme.