BackgroundTuberculosis (TB) is a major public health problem that accounts for almost half a million human immunodeficiency virus (HIV) associated deaths. Provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB in HIV infected individuals. However, in Ethiopia, the coverage and implementation of IPT is limited. The objective of this study is to compare the incidence rate of TB, TB-free survival time and identify factors associated with development TB among HIV-infected individuals on pre-ART follow up.MethodsA retrospective cohort study was conducted from January, 2008 to February 31, 2012 in Jimma hospital. Kaplan-Meier survival plots were used to calculate the crude effect in both groups on TB-free survival probabilities and compared using the log rank test. A Cox proportional hazard model was used to identify predictors of TB.ResultA total of 588 patients on pre-ART care (294 IPT and 294 non-IPT group) were followed retrospectively for a median duration of 24.1 months. The median CD4+ cell count was 422 cells/μl (IQR 344 – 589). During the follow up period, 49 individuals were diagnosed with tuberculosis, giving an overall incidence of 3.78 cases per 100 person year (PY). The incidence rate of TB was 5.06 per 100 PY in non-IPT group and 2.22 per 100 PY in IPT user group. Predictors of higher TB risk were: being on clinical WHO stage III/IV (adjusted hazard ratio (AHR = 3.05, 95% confidence interval (CI): 1.61, 5.81); non-IPT user (AHR = 2.02, 95% CI: 1.04, 3.92); having CD4+ cell count less than 350 cells/μl (AHR = 3.16, 95% CI: 1.04, 3.92) and between 350–499 cells/μl, (AHR = 2.87; 95% CI: 1.37 - 6.03) and having episode of opportunistic infection (OI) in the past (AHR = 2.41, 95% CI: 1.33-4.34).ConclusionIPT use was associated with fifty percent reduction in new cases of tuberculosis and probability of developing TB was higher in non-IPT group. Implementing the widespread use of IPT has the potential to reduce TB rates substantially among HIV-infected individuals in addition to other tuberculosis prevention and control effort in resource limited settings.