The potential for Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) dipstick tests to predict antimalarial treatment failure was investigated in a prospective study in Thailand of 38 patients admitted with severe malaria and 54 hospitalized with uncomplicated P. falciparum infections. Of these, 40 had subsequent recrudescence of their infections. Overall, 89% of patients with severe malaria and 61% of patients with uncomplicated malaria had positive PfHRP-2 dipstick tests for > 2 weeks following the start of treatment. Persistence was correlated positively with admission parasite counts, PfHRP-2 intensity scores and disease severity. PfHRP-2 tests which remained positive for > 2 weeks and PfHRP-2 reactive intensity scores on admission, at day 7 and day 14 did not predict treatment failure independent of admission parasitaemia. Freezing and thawing the blood samples did not significantly affect PfHRP-2 results tested by the dipstick technique. The PfHRP-2 dipstick test provides a useful indicator of recent severe malaria, but does not predict the therapeutic response.