A village-scale trial on the efficacy of mosquito nets treated with a tablet formulation of deltamethrin (K-OTAB®) against malaria in comparison to untreated nets or no net was conducted in Sundargarh District of Orissa, India, which is characterized by perennial transmission with Plasmodium falciparum accounting for more than 80% of malaria cases. Three villages with similar topographical and epidemiological situations were selected and randomly assigned to 3 arms of the study: treated net, untreated net, and no net. Distribution of nets, based on a sleeping pattern survey, was carried out to cover 100% of the population in treated-net and untreated-net villages. Longitudinal and cross-sectional surveys were conducted to measure malaria incidence, prevalence, and splenomegaly. Malaria incidence was reduced by 64.3% in the village with treated nets, 45.2% in the village with plain nets, and 21.4% in the control village without nets. Comparison of malaria incidence data after 1 year of intervention showed significant difference between villages with treated net vs. untreated net (P < 0.05) and treated net vs. no net (P < 0.005). The incidence of clinical attack rate due to P. falciparum was significantly lower in the population using treated nets than in those using untreated nets and no nets. However, no age-specific protective efficacy of treated nets or untreated nets was observed. A significant reduction occurred in spleen rate and parasite rate in children aged 2–9 years using treated nets or untreated nets. An overall significant reduction was found in parasite rate in the total population using treated and untreated nets as compared to nonusers.