We compared two dose forms of artemisinin derivatives, dihydroartemisinin suppository (DHA) and intramuscular artemether (ART), in children 6 months to 10 years of age with moderately severe malaria for which oral therapy was not appropriate. Children were randomly allocated to receive three daily doses of DHA or ART followed by a single oral dose of sulfadoxine-pyrimethamine on the third day of both treatment regimens and were monitored for parasitologic and clinical response for 14 days. At enrollment, parasite density was 1,640-523,333/microL (geometric mean parasite density [GMPD] = 58,129/microL) in patients treated with DHA, whereas that for children who received ART was 1,440-559,400/microL (GMPD = 60,387/microL). Mean parasite and fever clearance times were similar in both groups. Days 14 and 28 parasitologic cure rates were 100% (34 of 34) and 96.2% (25 of 26) versus 96.2% (25 of 26) and 91.7% (22 of 24) for children treated with DHA and ART, respectively. In conclusion, both treatment regimens were efficacious and well tolerated.