Mangifera indica, Alstonia boonei, Morinda lucida and Azadirachta indica (MAMA) decoction, commonly prepared and used in Nigeria from 1:1:1:1 ratio of Mangifera indica L. (Anacardiaceae), Alstonia boonei De Wild (Apocynaceae), Morinda lucida Benth (Rubiaceae), and Azadirachta indica A. Juss (Meliaceae) leaves, plus four new variants of this combination were subjected to three in vivo antimalarial test models using chloroquine-sensitive Plasmodium berghei berghei to determine the most active under each of the test models. Using the original formulation, MAMA (1:1:1:1) which gave ED50 and ED90 of 101.54±2.95 and 227.18±2.95, respectively, as reference for comparison, MAMA-1 (1:2:2:2), with 79.58±1.30 and 170.98±1.30, gave significantly (p<0.05) higher survival at 85 and 340 mg/kg when 80 % of the mice survived for 15.6 and 17.8 days, respectively, while MAMA-2 (2:1:2:2), with 83.57±1.93 and 164.23±1.93, gave comparable survival except at 170 mg/kg with 60 % survivors for 12 days. MAMA-1 and MAMA-2 were the best curative formulations with MAMA-1 giving additional prophylactic activity. MAMA-3 (2:2:2:1) with 98.70±0.91 and 220.17±0.91, gave comparable (p>0.05) survival at 85 mg/kg with 60 % survival for 13.2 days and significantly higher survival at 42.5 mg/kg for 17 days with 40 % survival. Both MAMA and MAMA-3 were the best chemosuppressive formulations plus additional curative activities. MAMA-4 (1:1:2:2), the best prophylactic formulation with 94.87±2.43 and 201.20±2.43 gave significantly higher (p<0.05) survival at all doses except at 21.25 mg/kg which gave 60 % survival up to 10 days. Thus, the antimalarial therapy desired, following appropriate diagnosis, whether prophylactic, chemosuppressive or curative would determine which of the MAMA decoction formulations to be prescribed. This phenomenon of formulary optimization may also be applied to other pharmacological activities.