OBJECTIVES:: Breast cancer is the most prevalent cause of cancer mortality. Recent data from the randomized controlled trial of targeted intraoperative radiotherapy-alone (TARGIT-A) has confirmed that, in women with early breast cancer, the technique of intra-operative radiotherapy (IORT) using the TARGIT technique is safe and as effective as conventional external beam radiotherapy (EBRT). We sought to conduct an economic evaluation of the IORT to inform reimbursement policy decisions and its implementation in usual practice in Brazil. METHODS:: A state transition Markov model was developed using decision analysis software TreeAge Pro Healthcare 2015 to capture the costs and outcomes of the TARGIT-A compared with EBRT. Evidence from the TARGIT-A trial was used to inform the model structure and incorporated disease progression as various model health states. Model outputs were represented in terms quality adjusted life years (QALYs), cost and incremental cost-effectiveness ratio. The outcomes were simulated for competing strategies for a time horizon of 10 years. Analysis was conducted in accordance with the published international and Brazilian pharmacoeconomic guidelines and Brazilian health care payer’s perspective was adopted. To address the uncertainty about the clinical effects of treatment, one way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed. RESULTS:: Discounted EBRT and IORT costs for the time horizon of 10 years were R$ 5138 and 6867 respectively. IORT gained 0.16 incremental QALY as the discounted QALYs gained by EBRT were 6.93 and by IORT were 7.08. The ICER calculated was R$ 11077 per QALY. Model results were robust to parameter uncertainty. CONCLUSIONS:: TARGIT-A is a cost-effective strategy to treat early breast cancer patients in Brazil. Implementation of this one-off radiation treatment could improve quality of life by sparing patients from the protracted course of EBRT, improve compliance and save valuable health care resources.