BACKGROUND: The leaves of the shrub Vernonia amygdalina Del (Compositae) are widely used in Africa to treat malaria. It is widely available, accessible, and affordable in many remote areas that do not have ready access to modern medicines. INTERVENTION: This study examined the efficacy and safety of an infusion of fresh V. amygdalina leaves for the treatment of uncomplicated malaria in patients aged 12 years and over. OUTCOME MEASURES: The primary outcome measure was an adequate clinical response. The secondary outcome measure was incidence of adverse events, assumed to be side-effects of the medicine. RESULTS: The remedy was associated with an adequate clinical response (ACR) at day 14 in 67% of cases. However, complete parasite clearance occurred in only 32% of those with ACR, and of these, recrudescence occurred in 71%. There was no evidence of significant side-effects or toxicity from the medication. There was a trend toward a reduction in hemoglobin between day 0 and day 28, although this did not reach statistical significance. CONCLUSIONS: Further studies are needed to determine whether the efficacy can be improved by increasing the dose, changing the preparation, or adding other antimalarial plants.