Background: The worldwide increased difficulty of anthelmintic resistance (AR), calls for an enhanced and standardized implementation of early detection of AR. This study aims to determine efficacy of anthelmintic drugs against Haemonchus contortus and Trichostrongylus columbriformis in sheep in Ada’a district in Ethiopia. Methods: Structured questionnaire and In vitro studies were conducted to evaluate the efficacy of different anthelmintic brands in serial dilutions of 1.0, 0.5, 0.25, 0.125, and 0.0625?g/ml. In vitro egg hatch test (EHT) assay, One hundred (100) eggs per well of Haemonchus. contortus and Trichostronglus. colubriformis were incubated with the drugs at 270C for 48 hours. In the Larval motility test, 50 infective larvae (L3) of parasites mixed with the drug of choice and incubated at 250C for 24hrs after which motile and non-motile worms were counted. In the adult motility test, 15 adult H.contortus per well were mixed with the test drugs and incubated at 370c for 10 hours while each test performed in triplicates. Results: The tested anthelmintic brands significantly showed concentration-dependent responses on eggs, larvae, and adult parasites. The Effective Concentration (EC50) result of EHA was found to be significant only for China (CN) brand of albendazole against both Trichostronglus. colubriformis (0.087µg) and Haemonchus. contortus eggs (0.017µg); whereas the EC50 test result on levamisole, brands indicated that East Africa (EA) brands (0.057µg) were found to be significantly effective against infective stages (L3) of Trichostronglus. colubriformis; whereas both brands of East Africa (EA) and India (IN) were significantly effective against both Haemonchus.contortus L3 (0.058µg) and L3 of Trichostronglus. colubriformis (0.048µg). The EC50 of ivermectin was showed a significant difference against both parasites isolates respectively within China brands for L3 of H. contortus and T. colubriformis and Indian brands for L3 of T. colubriformis. However, the EC50 done for tetramisole brands were suggested a lower efficacy of IN brands (5.576µg) than CN brands. Conclusions: China origins of the tested albendazole (ABZ), ivermectin (IVM), and tetramisole (TTM) brands were found to be more effective against eggs, infective stages (L3), and adults of the parasites concerned: On the other hand, LEV from East Africa Company is proven effective against L3 of both parasites whereas LEV and IVM from Indian origin are effective only against L3 of one species at acceptable concentration.