Introduction: Adverse drug reaction (ADRs) defined as: any unintended adverse response to a rndrug occurring at a therapeutic dose and resulting in either death, drug withdrawal, change in thernadministration of the frequency or dose of the drug, is one of the major concerns about SLDs torntreat MDR-TB. Hypothyroidism, liver toxicity, renal dysfunction and electrolyte disturbancesrnhave been reported among the prevalent ADRs during MDR-TB treatment. However, thesernADRs had not investigated in Ethiopia. rnObjectives: The aim of this study was to investigate the sero- prevalence of adverse drugrnreactions (ADRs) and associated risk factors among MDR-TB patients with second line drugs. rnMethods: this prospective, observational cohort study was carried out from August 2013 to Aprilrn2014 in Mekellle Hospital. 68 confirmed pulmonary MDR-TB patients by Tigray RegionalrnLaboratory were followed and evaluated for ADRs development during the study period.rnRoutine laboratory test according to ADRs monitoring schedule was done in Ayder ReferralrnHospital in collaboration with Mekelle Hospital. Demographic and clinical information werernextracted from standardized clinical files. rnResults: There were 67.6% male and 32.4% female patients. The mean patient age was 32.62 Â±rn(11.173) years. Among the 68 patients screened for adverse drug reactions, electrolyte relatedrnabnormality (hypokalemia 47/68(69.11%), hypomagnesaemia18/68(26.47%) and hypocalcaemiarn8/68(11.76 %) was 83.80%, nephrotoxicity 22/68(32.35%), hypothyroidism16/68(23.53%) andrnhepatotoxicity 10/68(14.71%) were recorded. rn Conclusions: High rate of hypokalemia, nephrotoxicity, hypothyroidism and hepatotoxicity wasrnobserved in this cohort. This is a treatable and reversible; however, it may go undiagnosed in thernabsence of regular monitoring. Care providers should not wait for clinical symptoms, as this risksrncompromising treatment adherence. Electrolyte related abnormalities and renal toxicity was thernmost prevalent among others. Higher magnitude of ADRs was observed among older, femalesrnand HIV co-infected patients on ART/anti-TB.