OBJECTIVES: To compare and rank available ACT regimens for treating PF malaria METHODS: We searched PubMed, Embase, and the Cochrane Central systematically for the randomized control trials (RCTs) of ACT regimen for treating PF malaria. Network meta-analysis (NMA) was performed to estimate risk ratio (RR) and 95% confidence interval (CI) from both direct and indirect evidences. We then ranked the comparative effects of all interventions with the surface under the cumulative ranking (SUCRA) probabilities. Inconsistency between direct and indirect estimates was statistically assessed globally. Primary outcome was adequate clinical and parasitological response (ACPR) at 28 days. Secondary outcomes were ACPR at 42 days, and serious adverse events. RESULTS: A total of 28 RCTs with 16 409 patients were included. The most commonly investigated regimens were artemether plus lumefantrine (ATM+LMF), dihydroartemisinin-piperaquine (DHDATN+PPQ) and artesunate plus amodiaquine (ATS+AMQ). DHDATN+PPQ was associated with a significantly higher ACPR than artesunate plus mefloquine (RR 1.01, 95% CI 1.00 to 1.03), ATM+LMF (RR 1.02, 95%CI 1.01 to 1.04), artesunate plus chlorproguanil and dapsone (RR 1.12, 95%CI 1.07 to 1.16) but not significantly higher than artesunate plus mefloquine (RR 1.00, 95% 0.99 to 1.03). CONCLUSIONS: This NMA suggests that DHDATN+PPQ was the most effective ACT regimens and should be preferred as first-line regimens against PF malaria.