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In terms of drug resistance Bangladesh acts as an important gateway to the Indian Subcontinent. However, little is known about the current status of drug resistance in this country. The aim of this study was therefore to determine the therapeutic efficacy as well as in vitro drug sensitivity of quinine for 3 days plus a single dose of sulfadoxine/pyrimethamine (Q3F), an affordable alternative to the previously used chloroquine, for the treatment of uncomplicated falciparum malaria. Sixty-three patients were enrolled in the study; the overall cure rate in a 42-day follow-up after PCR adjustment was 87.3% (95% CI: 77.6–94.1). One patient was classified as early treatment failure (1.7%, 95% CI: 0.0–8.9%); 6 patients (10%; 95% CI: 3.8–20.5%) had late treatment failures within a median time of 27 days. HRP2 in vitro drug sensitivity tests were performed on all samples. Significantly higher (P = 0.008) in vitro IC50s for pyrimethamine in treatment failures reflect the somewhat compromised drug sensitivity to this drug. These data suggest that the combination of 3 days of quinine with a single dose of sulfadoxine/pyrimethamine is an interesting and affordable alternative as long as or whenever ACT is not available.