Tsetse transmitted animal trypanosomosis is an economically devastating disease in Sub Saharan Africa where trypanocidal drug treatment is the mainstay of control but their rnefficacy is hampered because of the widespread occurrence of drug resistance. The rnpresent study conducted from March to June of 2014 in young zebu cattle was to rndetermine the drug sensitivity of T vivax isolates from selected tsetse infested and tsetse rnfree areas of Northwest Ethiopia and also to look for hematological profiles improvement rnafter treatment. A total of tluÂ·ee isolates one from tsetse infested and two from tsetse free rnareas were used. A prospective study and randomized controlled block design was rnapplied to the experimental animals together with preliminary questionnaire survey on rndrug usages. The study revealed that one isolate from tsetse free area was resistant to rn7mg/kg of DA. The finding of one relapse from the tsetse isolate to 1mg/kg of ISM is rnhighly indicative that more relapses could be found if more isolates were used. The rndecrease in packed cell volume and hemoglobin concentration improvements was more rncommon in breaktlu-ough infections. Results of the experiment on the low efficacy of the rndrugs were supported by respondents of questiolU1aire survey. In conclusion, drug rnresistance is a tmÂ·eat in both areas and the situation is magnified in the non-tsetse areas so rnthat control of the disease should be an integrated approach. Moreover, the use of rnsanative pair with DA and ISM in accordance with the reported drug resistance is rnimpOliant to reduce the problems in the study sites. Fmihermore, extensive data on rntrypanocidal drug sensitivity tests on more T. vivax isolates using advanced molecular rntechniques is essential.