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The impact of vector control measures on the evolution of antimalarial drug resistance is an important issue for malaria control programs. We investigated whether the in vivo efficacy of chloroquine (CQ) in children aged 6–59 months with uncomplicated malaria differed in 9 villages that had benefited from long-term use of insecticide-treated curtains (ITCs) and in 9 nearby non-ITC villages. We also compared the prevalence of genetic markers of resistance to CQ and sulfadoxine-pyrimethamine (SP) between the two groups of villages. The study enrolled 1,035 children with uncomplicated malaria and 231 infected but asymptomatic children. After taking account of re-infections, the proportions of children who experienced clinical failure after treatment with CQ were 14% and 19% in ITC and non-ITC villages, respectively (OR = 0.68; 95% CI: 0.39, 1.18). Parasitologic failure was observed in 49% of children in ITC villages and 58% of children in non-ITC villages (OR = 0.71 95%CI: 0.44, 1.13). The proportion of symptomatic children who harbored parasites carrying the pfcrt-76T allele was 43% in ITC villages and 40% in non-ITC villages (OR = 1.09; 95%CI: 0.80, 1.50). The pfmdr1-86Y allele was detected in 31% and 29% of children in the two groups of villages (OR = 1.14; 95%CI: 0.75, 1.72). Triple mutations in the dhfr gene were observed in 12% of children in both groups. No double mutations in the dhps gene were observed. Similar results were observed in asymptomatic children. In this setting, ITC use was not associated with increased circulation of parasites resistant to standard antimalarial drugs, or with a greater risk of treatment failure among children less than 5 years of age.