MDR-TB has emerged in Israel following an immigrations wave from the Former Soviet Union (FSU) and Ethiopia. The purpose of this study was to outline characteristics and outcome of hospitalized MDR-TB patients. We retrospectively summarized charts of MDR-TB patients hospitalized in the national referral tuberculosis centers from January 2000 to December 2005, and followed them for 2 years. One hundred thirty-two patients were identified with a median age of 40 years and male predominance (77%). The majority of the patients were immigrants from FSU (83%) and Ethiopia (7.6%). They were characterized by alcohol (25.8%) and IV drug abuse (23.5%), presented with advanced disease manifested by hypoalbuminemia (50.8%) and smear positivity (70.5%). Cure was achieved in 50.3% and 30.4% died. Factors independently associated with death were patients’ age (OR = 1.036 for each year, 95%CI 1.0–1.1, p = 0.014), hypoalbuminemia (OR = 2.95, 95%CI 1.1–7.6, p = 0.025), smear positivity at diagnosis (OR = 3.7, 95%CI 1.2–11.4, p = 0.023), alcohol abuse (OR = 4.8, 95%CI 1.7–13.7, p = 0.004) and XDR-TB resistance pattern (OR 8.3, 95%CI 1.5–44.6, p = 0.014). This study brings out the poor prognosis of a highly vulnerable immigration population. Efforts should be focused on earlier diagnosis and treatment in a well controlled hospital environment and to professional support groups to attend to this population’s special needs.