Vector-control measures are a component of integrated malaria control strategies. After evaluation in phase III pilot studies, these measures are currently being deployed in many endemic malaria zones. Their effectiveness must be evaluated under actual conditions of use but it is not ethically acceptable to use unexposed individuals for control groups. In a attempt to overcome this problem, a case-control study was undertaken to evaluate the effectiveness of long-lasting insecticide treated mosquito nets (LLITN) against clinical malaria attacks due to Plasmodium falciparum in an endemic area of southern Benin. During a 4-month period (July to October 2008), 35 clinically documented cases of uncomplicated malaria (fever + parasite density > 3000/microL) were diagnosed in children less than 5 years old from 6 villages in the Tori Bossito medical district. The parents of these children were interviewed at the same time as the parents of 181 children randomly selected from the same 6 villages. A total of 115 of the randomly selected children who had not been feverish during study period were used as controls. The proportion of children having consistently slept under LLITN throughout the study period was 46% in the case group and 78% in the control group (OR=0.32, 95%CI: 0.15-0.71). These data show that the LLITN provided a significant level of protection, i.e., 68% (IC95%: 29%-85%). This case-control study shows that vector control measures can be effectively evaluated after deployment in population. The limitations of this methodology are discussed.