Emamectin benzoate and spinetoram are two important and promising new insecticides in caterpillar lepidoptera larvae/larvae control. The toxicity of these compounds against larvae of cotton leafworm (CLW), Spodoptera littoralis (Boisd.) was compared using topical application and feeding techniques. The persistence/residual efficacy under field conditions was also investigated. Based on the LD50 values against 4th instar larvae, emamectin benzoate proved to be better than spinetoram by 31516 fold. The LD50 values of emamectin benzoate, cypermethrin, methomyl, chlorpyrifos, pyriproxyfen, profenofos, chlorpyrifosmethyl, abamectin, spinetoram, spinosad and imidacloprid were 0.0019, 0.0039, 0.03, 1.62, 3.13, 3.38, 4.00, 9.38, 59.88, 558.25 and 37384.38 µg a.i/ g larvae, respectively. The 3rd instar larvae showed higher susceptibility toward emamectin benzoate than spinetoram by 1551 and 41 times after 2 days post-treatment using cotton and castor bean, respectively. Two days post- treatment, the persistence of emamectin benzoate decreased gradually and significantly. After spraying cotton, the mortality percentages were 98.00, 70.00, 36.67 and 0.00 % after 0, 3, 6 and 10 days, respectively. However, the mortality % of this insecticide in castor was 91.11, 93.33 and 0.00 % after 0, 3 and 6 days respectively. In spinetoram, these percentages in cotton and castor were 96.67, 3.33, 3.33 and 0.00, 2.86, 0.00 after 0, 3 and 6 days. Our investigation recommended that emamectin benzoate is one of the best bio-insecticides in controlling CLW larvae infestations in cotton fields.