OBJECTIVES: Case of latent tuberculosis has increased over the years as many from developing countries travel to the US. This study compared three CDC recommended regimens (Isoniazid, rifampin, and rifampin-pyrazinamide) for latent tuberculosis by conducting a cost effectiveness analysis taking into consideration adherence rates and incidence of adverse drug events. METHODS: A systematic literature review pertaining to cost-effectiveness studies involving these three regimens from 1990 to 2009 was conducted using Pubmed. A decision tree model was developed to infer the most cost-effective regimen using data form randomized clinical trails.  Cost in the model included drug cost, primary physician visit cost, follow up physician visit cost, and adverse drug events costs and were obtained from published literature. Rash and hepatotoxicity were the adverse events considered in the model as these were highly associated with these treatment regimens. Completion rate (adherence to the medication regimen) was the outcomes evaluated. One-way sensitivity analyses were conducted by varying various costs by 10% to check for the robustness of the model. RESULTS: The base-case analysis revealed rifampin-pyrazinamide to be the most cost-effective regimen. The one-way sensitivity analysis indicated the results to be robust. The total cost for treatment with isoniazid was $1360.53, rifampin was $2111.34, and rifampin-pyrazinamid combination was $978.69. The adherence rate to isoniazid treatment was 53% as compared to rifampin and rifampin-pyrazinamide which was found to be 70% and 81% respectively. Rifampin-pyrazinamide associated with hepatotoxicity (4%) as compared to isoniazid (1.5%) and rifampin (3%) still proved cost effective. ICER for switching the treatment from rifampin-pyrazinamide regimen to isoniazid was $86.87 and to rifampin was $237.02. CONCLUSIONS: These analyses based on the data from randomized clinical trial, shows that rifampin-pyrazinamide was indicated to be the cost effective treatment for patients with latent TB, as compared to isoniazid and rifampin alone.