Background: The World Health Organization (WHO) recommends Artemisinin-based combination therapy (ACTs) for the treatment of uncomplicated malaria, but multiple products are now available. In preparation for the 2008 revision of the WHO Malaria Treatment Guidelines, the Malaria Technical Guidelines Development Group (TDG) requested a summary of head to head ACT comparisons, with GRADE assessment. Objectives: To summarize the comparative effects of ACT antimalarial drugs for treating uncomplicated P. falciparum malaria; and to prepare GRADE tables for the TDG Panel. Methods: A standard Cochrane search strategy was used to identify relevant randomized controlled trials, and standard Cochrane review methods were used. Primary outcome data were analyzed in line with the WHO ’Protocol for Assessing and Monitoring Anti-malarial Drug Efficacy’ and drugs compared using risk ratios (RR) and 95% confidence intervals. GRADE methods were adapted with advice from the TDG Panel. The analysis was restricted to the five currently recommended antimalarial combinations and the most promising new product dihydroartemisinin-piperaquine. Results: Forty-seven trials met the inclusion criteria. All five ACTs were shown to have failure rates of < 10% in line with WHO recommendations. Dihydroartemisinin­piperaquine was shown to be at least as effective at reducing treatment failure as the other recommended combinations. GRADE assessments were prepared and presented to the panel, but the panel needed the Cochrane review to help understand and interpret the GRADE assessments. Conclusions: The review results show that dihydroartemisinin-piperaquine should be added to the list of recommended ACTs. The experience with GRADE showed that there was a need to refer back to the Cochrane reviews during the discussions. Given a dialogue with the WHO, it is possible for Cochrane Review Groups to prepare new reviews for TDG Panels, but this needs at least one full time, salaried author.