Abstract: AIM: To observe the comparative effects of pyronaridine/sulfadoxine pyrimethamine with single dose or two day regimens in combination with primaquine in 2 endemic areas of multidrug resistant falciparum malaria in Hainan Island. METHOD: A total of 100 patients with acute falciparum malaria were randomly divided into 2 groups. Group A was orally administered with a single dose of pyronaridine(PND) 500 mg/sulfadoxine(S)1 000 mg and pyrimethamine(P) 50 mg composite plus primaquine(Pq)22.5 mg, 24 hours later Pq 22.5 mg was given again; and Group B received a dose of PND 400 mg/S 500 mg and P 25 mg composite plus Pq 22.5 mg daily for 2 days. RESULTS: The average fever subsidence time of groups A and B was 39.8±27.2 and 42.1±20.5, the asexual parasite clearance time was 46.9±13.3 and 51±14.1 ( P 0.05), the rates of asexual parasite eliminated within 24 hours were 80% and 78%, respectively; the asexual parasite clearance rate within 28 days of both groups was 100%. Gametocytes were cleared within 21 days. The side effects were mild, but hemolysis reaction occurred in 3 cases of each group. CONCLUSION: Both presented regimens could cure multidrug resistant falciparum malaria.