We investigated the relationship between the two main molecular markers for chloroquine resistance (Pfcrt T76 and Pfmdr-1 Y86) and the clinical efficacy of amodiaquine in Burkina Faso. Before treatment, the prevalence of Pfcrt T76, Pfmdr-1 Y86 or both mutations in the same infection was significantly higher in patients who experienced a recrudescence than in those who successfully responded to the treatment. Therefore, these two molecular markers could be useful in monitoring amodiaquine resistance, particularly in countries where this drug is used in combination with artesunate as first- or second-line treatment.