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: Objectives We sought to identify chloroquine-resistant Plasmodium falciparum parasites among 66 travellers who presented in the UK with malaria. : Methods A multiplex real-time PCR assay was devised to identify wild-type and two distinct chloroquine-resistance-associated alleles of the pfcrt gene. : Results Those with documented use of chloroquine/proguanil prophylaxis were more likely to carry parasites with resistance-associated alleles of pfcrt than were patients who had been using antimalarials other than chloroquine (92.9% versus 37.5%; P = 0.011). We also found evidence that people reporting optimum compliance with chloroquine prophylaxis during malaria exposure were more common among malaria cases than were those reporting optimum compliance with other regimens (OR 3.85, 95% CI 1.61–9.69; P = 0.0008). : Conclusions Chloroquine, known to be failing as therapy for falciparum malaria worldwide, is also failing to provide adequate malaria prophylaxis for travellers. [ABSTRACT FROM AUTHOR]