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Use of an insecticide-treated net (ITN) is now the central focus for the Roll Back Malaria campaign, and disease-endemic countries have embarked on large-scale ITN distribution programs. We assessed the impact of an ITN social marketing program on clinical malaria in children less than five years of age. A case-control study was undertaken at Ndirande Health Center in the peri-urban area of the city of Blantyre, Malawi. Cases were defined by an axillary temperature ≥ 37.5°C or a history of fever within the last 48 hours and a positive blood smear for Plasmodium falciparum. The individual effectiveness of ITN use was 40% (95% confidence interval [CI] = 10–60%) when cases were compared with clinic controls and 50% (95% CI = 0–60%) in comparison with community controls. With ITN coverage of 42%, the community effectiveness of this program was estimated to range from 17% to 21%. This represents 1,480 malaria cases averted by the intervention in a population of 15,000 children. Our results show that the benefits of ITN social marketing programs in reducing malaria are enormous. Targeting the poor could increase those benefits.