Artemisinin combination therapies are considered the mainstay of malaria treatment, but paediatric friendly formulations for the treatments of infants are scarce. We aimed to evaluate the efficacy and safety of a new dispersible tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim(R)) in the treatment of infants with uncomplicated P. falciparum malaria.Reported here are the results of a large phase II, randomized, open label, multicenter trial conducted in African infants (6-12 months of age) from Mozambique, Burkina Faso, The Gambia, DR-Congo and Tanzania. Primary efficacy endpoint was the PCR-corrected Adequate Clinical and Parasitological Response (ACPR) at day 28. Analysis was performed for the Intention-To-Treat (ITT) and Per-Protocol (PP) populations.Two-hundred and one patients received the dispersible tablet formulation and 99 the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPR was 86.9% (ITT) and 98.3% (PP) in the dispersible tablet group, and 84.9% (ITT) and 100% (PP) in the crushed tablet group. At day 42, it was 85.9% (ITT) and 96.5% (PP) in the dispersible tablet group, and 82.8% (ITT) and 96.4% (PP) in the crushed tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences (p=0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of Adverse Events and was consistent with that expected in African infants with malaria.A standard three-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants, and has a comparable safety profile.