Background: Tuberculosis (TB) remains a serious public health problem, worsened by thernemergence and spread of drug resistance particularly multi-drug resistance that threat global TBrncontrol. Data obtained from KAP survey is essential to plan, implement and evaluate Advocacy,rnCommunication and Social Mobilization (ACSM)work.rnObjectives: The aim of this study was to assess the magnitude of drug resistance pattern ofrnM.tuberculosis, knowledge, perception and practice of patients` towards TB in Eastern AmhararnRegion, North East Ethiopia.rnMethods: A cross sectional survey was conducted among new and re-treatment patients (age >rn18 years old) from September 2010 to February 2011. A structure and pre-validaternquestionnaires was used to collect data. Primary isolation and DST were carried out on egg basedrnLJ media using indirect proportion method. Chi-Square and multivariate logistic regression wasrnused.rnResults: Out of 230 study participants for DST, 165 were new cases while 65 were previouslyrntreated cases. From these, 66.5% of isolates were sensitive and 4.4% resistance to four f irst linernanti-tuberculosis drugs (HRSE) while the remaining 33.5% was resistance to at least for singlerndrug. MDR-TB was detected in 6.5 % isolates, of which 4.4% were resistance to all four firstrnline drugs. Overall resistance to S, R, H and E was found in 27 % (62), 10 % (23), 17.8 % (41),rnand 6.5 % (15) respectively. Mono resistance was found in 17.4 % (40) of all isolatesrnAmong new cases primary drug resistance for one or more drugs was observed in 23.6 % (39)cases. Primary MDR-TB was found in 3 (1.81%) cases. Similarly among previously treated casesrnresistance to any drug was found in 58.5 % (38) cases. MDR-TB in previously treated cases wasrnfound in 18.46 % (12) Cases; the highest being in failure cases 9.23% (6).rnMore over the mean and median knowledge score of respondents about PTB was 6.81 and 7rnrespectively. Majority (53.6%) of study subjects had poor knowledge score, feels not wellrninformed about TB and had several misconceptions that need to be clarified. Majority (66.6%)ofstudy subjects heard about TB for the first time from health workers. Of study participants,rn79.9% mentioned that TB transmits by respiratory droplets through coughing and sneezing andrnprevents by covering mouth and nose (66.6%). The four common symptoms mentioned byrnrespondents were cough (65.6%), weight loss (33.2%), cough > = 2 weeks (32.7%) and shortnessrnof breath (29.4%). About half of respondent not knew current free cost of TB diagnosis andrntreatment. Majority of respondents also worried about the disease due to it might transmits torntheir family, might not be cure, social interact (fear of stigma) and unable to do work. Cost (69.9rn%) and difficulties in transportation (54.5 %) mentioned as the main reason for their delaines t ornseeking care.rnPrevious drug exposure and 1rn+rnbacterial load independently contribute for the development ofrndrug resistance TB strains. Similarly Illiteracy, rural residence, non-previous history ofrncontracting TB, experiencing self treatment option, and delayed frequency of visit werernindependent predictor of low knowledge score.rnConclusion: Drug resistance TB particularly MDR-TB is an emerging problem in new and retreatmentrnrnpatients in our study area. Majority of respondents also had poor knowledge andrnseveral misconceptions that need to be clarified. Hence, it is essential to address the problems ofrndrug resistance through establishing good TB control program including DOTS plus service andrnraise KAPs` of patients through establish proper IEC pathway to indicate the level of severityrnand to create proper awareness about its cause, transmission, prevention and availability ofrnservice.