We reported two cases of complicated falciparum malaria who had poor response to artesunate with delayed parasite clearance times. They were splenectomized patients who were treated with high doses of artemisinin derivatives. Our cases showed the importance of the spleen in the clearance of malaria parasites and had different clinical outcome, one fatal and one recovery. The host factors, the parasitemia count, the quality of antimalarial chemotherapy and blood level of the antimalarial drugs must be considered in relation to the causes of the delayed clearance of parasitemia.