In 2002 an antimalarial drug resistance survey was carried out in a seasonally endemic area of Vietnam. Sulfadoxine/pyrimethamine (S/P) was the standard treatment recommended for uncomplicated Plasmodium falciparum malaria in that area at the time. Early or late treatment failure as defined by WHO was observed in 14.9% (7/47) of patients. Molecular analysis of treatment failure isolates identified that 5/6 carried two or more dhfr and dhps polymorphisms associated with S/P resistance. Chloroquine resistance-associated polymorphisms occurred in 38.5% (15/39) of the isolates. These results support the move to artemisinin-based combination therapy for malaria in Vietnam.