OBJECTIVES Whole-breast external beam radiotherapy (EBRT) is normally given over 3-6 weeks after lumpectomy in early breast cancer patients to reduce recurrence and mortality. An individualised risk-adapted approach to adjuvant radiotherapy has been tested in the randomised TARGIT-A trial which tested the efficacy of one dose of radiation to tumour bed during lumpectomy. The objective of the present study was to assess the cost effectiveness of TARGIT-A in these patients.  METHODS A model based economic evaluation compared single dose TARGIT-A with current practice of EBRT in UK. A state transition Markov model approach was used to simulate the treatment outcomes in a time horizon of 20 years post-surgery. The primary outcome of interest was quality adjusted life years gained (QALY) and analysis was conducted from the health care payer’s perspective. To address decision uncertainty, probabilistic sensitivity analysis was performed. A discount rate of 3.5% was applied to future costs and effects.   RESULTS In the Base Case Analysis TARGIT-A was a dominant strategy yielding higher QALYs at a lower cost than EBRT. Discounted EBRT and IORT costs for the time horizon of 20 years were £ 20, 926 and £ 14, 461 respectively. Discounted incremental QALY gained by use of IORT was 0.0069. Model results were robust to parameter uncertainty and probabilistic results were similar to the deterministic results. Application of the net monetary benefit (NMB) framework revealed higher NMB for TARGIT-A in all Monte Carlo simulations. Cost effectiveness acceptability curves show that TARGIT-A is cost effective at various willingness to pay thresholds. CONCLUSIONS TARGIT-A is a cost effective strategy to treat early breast cancer patients in the UK. Implementation of this one-off radiation treatment within a risk-adapted approach could improve quality of life by sparing them from the protracted course of EBRT, improve compliance, prevent unnecessary mastectomies and save valuable NHS resources.