Objective  To compare the efficacies against uncomplicated falciparum malaria of chloroquine (CQ), amodiaquine (AQ), sulfadoxine–pyrimethamine (SP) and combinations of these inexpensive drugs.

Methods  We searched Medline, Embase, Cochrane CENTRAL Register of Controlled Trials, BIOSIS, Web of Science, African Index Medicus, DARE, Digital Dissertations and Current Controlled Trials for randomised or quasi‐randomised controlled trials conducted between 1991 and June 2004 regardless of language and geography. We also contacted malaria experts, searched reference lists, and contacted individual authors for unreported study characteristics and additional data. Unpublished data were sought and included in the analyses.

Results  Thirteen randomised trials (n = 4248) were identified and the summary relative risks of treatment failure at 28 days were calculated. There was marginal benefit in adding CQ to SP, compared with SP monotherapy (RR = 0.74, 95% CI 0.54–1.02). Combining AQ with SP was associated with a significantly lower risk of treatment failure than SP monotherapy (RR = 0.35, 95% CI 0.15–0.82) and AQ monotherapy (RR = 0.59, 95% CI 0.42–0.83). AQ plus SP was associated with a significantly lower risk of treatment failure than CQ plus SP (RR = 0.42, 95% CI 0.25–0.72). Serious adverse events were rare and did not increase with combination therapy.

Conclusion  Amodiaquine plus SP remains an efficacious, affordable and safe option for treating malaria in certain settings.