Background: Drug resistance in Mycobacterium tuberculosis complex remains major healthrnburden in human history and still is a major leading cause of death in developing countries. Earlyrndetection of all forms of drug resistance tuberculosis is a key factor to reduce and contain thernspread of these resistant strains. A better knowledge of the mechanisms of action of antituberculosisrnrndrugs and the development of drug resistance will allow identifying new drugrntargets and better ways to detect drug resistance. Drug Susceptibility test of certain drugs canrnalso be technically challenging, in resource limited areas and cost prohibitive.rnObjective: The objective of this study was to asses molecular and phenotypic drug resistancernPattern of common Mycobacterium tuberculosis complex species and associated mutation. rnMethods: A cross sectional study design was followed, the data was collected using standardrncheck list and sputum samples from a total 204 study individuals with bacteriologicallyrnconfirmed tuberculosis cases. Sputum samples was analyzed using conventional Tuberculosisrnculture and Identification followed by molecular and then phenotypic drug susptability test forrnboth first line and second line drugs was done as a gold standard to see the drug susptabilityrnpattern and associated mutations. Data was entered in to SPSS version 20 and export to STATArnversion 12 for analysis. Descriptive analysis and frequencies was used for analysis. Results: Out of 204 Clinical samples collected, Mycobacterium species were recovered from165rnin which 160 were Mycobacterium tuberculosis complex and the remaining 5 isolates were nontuberculosisrnrnMycobacterium species. Differentiation of Mycobacterium tuberculosis complexrnisolates was conducted by using genotype MTBC assay and the result revealed that all werernfound out to be M. tuberculosis. Out of 5 Non Tuberculosis Mycobacterium species: 2rnM.fortuitum, 2 M.intracellulare and 1 M.gordonae were identified. Among 160 species of M.rntuberculosis isolates 110(68.8%) and 50(31.2%) were susceptible and resistance to one of allrndrugs tested, respectively. Ninety-nine isolates were Multi drug resistance while 8(5%) isolaternwas Pre-Extensive drug resistance, whereas 1(0.6%) isolate identified as Extensive drugrnresistance. Out of genotypic resistance isolates highest frequency of mutation detected for katGrn86(92.5%) followed by rpoB (93(58.15%), 4(4.3%) inhA and4 (4.3%) gyrase genes. A total ofrn30(18.7%) isolates found to be discordant from this 12(7.5%) for Rifampicin, 16 (16%) forrnIsoniazid, 3(1.8%) for Fluoroquinolone and 3(1.8%) for Second line injectable drugs. rn rnConclusion: In conclusion, the present study findings in the phenotypic DST pattern showedrnthat the magnitude of drug resistant TB in the previously treated TB cases was higher asrncompared to new cases. Highest proportion drug resistance detected for INH followed by RIF,rnresistance for EMB and STM all so higher. Determining the yield of drug resistance TB usingrnboth Phenotypic and Molecular DST methods were recommended for programmaticrnmanagement of drug resistance Mycobacterium tuberculosis complex in Ethiopia.