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Introduction There are scarce data on the routine latent tuberculosis infection treatment (LTBIT) and factors associated with a non-completion in high tuberculosis burden countries. Therefore, in this study we aimed to evaluate the factors associated with non-completion of LTBIT. Materials and methods This was a non-matched case control study conducted at a University Hospital in Rio de Janeiro, Brazil. A total of 114 cases and 404 controls were enrolled between January/1999 and December/2009. Cases were close contacts who did not complete the LTBIT and controls were the contacts that completed it. Multivariate analysis was used to investigate risk factors associated with non-completion of LTBIT among contacts in two different periods of recruitment. Results Factors associated with non-completion LTBIT included: drug use (OR 23.33, 95% CI 1.83–296.1), TB treatment default by the index case (OR 16.97, 95% CI 3.63–79.24) and drug intolerance. TB disease rates after two years of follow up varied from 0.4% to 1.9%. The number necessary to treat to prevent one TB case among contacts was 116. Conclusions Non-completion treatment by the index case and illicit drug use were associated with not completing latent tuberculosis infection treatment and no tuberculosis disease was identified among those who completed latent tuberculosis infection treatment.