A new dose regimen of artesunate and amodiaquine (NDRAA) based on age or body weight range was compared with standard dose regimen of artesunate and amodiaquine (SDRAA) calculated according to body weight and with fixed-dose artesunate-amodiaquine (FDAA) and artemether-lumefantrine (AL) in 304 children afflicted by malaria aged 15 years or younger. In initial comparison (n = 208), children on NDRAA received 1-3 times amodiaquine per kilogram of body weight and 1-1.5 times of artesunate per kilogram of body weight compared with those receiving SDRAA. Parasite but not fever clearance was significantly faster in children who received NDRAA (19.4 ± 8.4 hours vs. 24.6 ± 15.5 hours, P = 0.003). Polymerase chain reaction-uncorrected cure rates on days 28-42 were also significantly higher in children who received NDRAA (P < 0.02 in all cases). Therapeutic responses in children younger than 5 years (n = 96) treated with NDRAA, FDAA, and AL were similar. Changes in hematocrit values and reported adverse events after commencing therapy were similar in those who received NDRAA and SDRAA. All drug regimens were well tolerated. NDRAA based on age or body weight range is simple, is therapeutically superior to SDRAA calculated according to body weight, and is as efficacious as AL in children younger than 5 years.