We report the case of an obese patient who experienced late failure on day28 of a well-conducted treatment with artesunate, followed by dihydroartemisinin-piperaquine (DHA-PPQ) for a severe P. falciparum malaria attack. The same P. falciparum strain was evidenced at day0 and day28. Genotypic and phenotypic resistance tests could not explain this treatment failure. The low plasma piperaquine concentration at failure may explain the poor elimination of residual parasites.