Current international guidelines recommend 6-9 months of isoniazid (INH) preventive chemotherapy to prevent the development of active tuberculosis (TB) in susceptible children exposed to Mycobacterium tuberculosis. However, this is dependent on good adherence, as shown by previous studies. This study was conducted to describe the outcome of screening of contact children aged 5 years or less with household exposure to an adult pulmonary TB index case to determine the prevalence and possible risk factors of infection among contact children and to determine the extent and outcome of adherence of contact children to unsupervised INH chemoprophylaxis for 6 months. A descriptive facility-based cross-sectional study was conducted from March 2009 to August 2010. Research settings were three of the National TB control program chest dispensaries (primary care facilities) in Alexandria, Egypt. Facility-based TB treatment registers of the previous 3 months were used to identify all new adult pulmonary TB cases. All children aged 5 years or less living in the same house as the index cases were identified and screened for TB. The contact children were given unsupervised INH preventive chemotherapy once active TB was excluded. Adherence to and outcome of preventive chemotherapy were followed up. Preventive chemotherapy consisted of unsupervised INH monotherapy for 6 months with monthly collection of tablets from the clinic. Adherence was documented after completion of the 6-month preventive treatment period. Adherence was considered reasonable if tablets were collected for more than 4 months, poor if collected for 2-4 months, and very poor if collected for less than 2 months. (a) Prevalence of infection and disease and the possible risk factors among contacts. (b) The extent and outcome of adherence to unsupervised INH chemoprophylaxis among contact children. (c) Factors behind poor adherence. In total, 197 adult TB index cases from 187 households were identified. In all, 297 children aged 5 years or less experienced household exposure, of whom 252 (84.9%) were fully evaluated. Tuberculin test was positive in 136 of the 252 child contacts (54.0%), of whom 130 were contacts of sputum-positive patients and six were contacts of sputum-negative patients. The important risk factors for transmission of TB infection were younger age, male sex, severe malnutrition, absence of BCG vaccination, contact with a sputum-positive adult who was a source case, household overcrowding, and exposure to environmental tobacco smoke. Thirty-three children were diagnosed and treated for TB at the baseline screening and 217 received preventive INH chemotherapy. Of the children who received preventive chemotherapy, only 36 (16.6%) completed at least 4 months of unsupervised INH monotherapy. During the subsequent follow-up period, eight children developed TB (secondary attack rate for TB disease was 3.7%), of whom four received no preventive chemotherapy and four were poorly adherent. The prevalence of TB infection and clinical disease among children in household contact with adult patients is high, and risk is significantly increased because of child contact, index patients and environmental factors. Adherence to 6 months of unsupervised INH chemoprophylaxis was very poor.