Objectives: Current international guidelines recommend 6-9 months of Isoniazid (INH) preventive chemotherapy to prevent the development of active tuberculosis in children exposed to smear positive tuberculosis (TB) patients. The aim of the present study was to evaluate the adherence to a six-month of supervised INH prophylaxis program and outcome in children with household exposure to an adult pulmonary tuberculosis index case in Varamin city, Tehran, Iran. Methods: This cross sectional study was conducted among household contacts in Varamin city, between 1997- 1998. All children <6 years old with a household contact with an adult pulmonary tuberculosis index case were screened for tuberculosis and given supervised INH preventive chemotherapy once active tuberculosis was excluded as planned. Adherence and outcome were monitored. Results: In total, 31 index cases and 128 household contact cases were identified; 23 (18%) children <6 years old experienced household exposure, who were fully evaluated. two children were treated for active tuberculosis and 15 (12%) children received preventive chemotherapy. All children completed 6 months of supervised INH prophylaxis with normal clinical examination in 3 and 6 months after beginning INH prophylaxis. No side effects (peripheral neuropathy or liver damage) were reported or observed within this study. Conclusions: Strategy of six months of supervised INH chemoprophylaxis is successful, particularly in children who are at a high risk to progress to disease following exposure.