OBJECTIVES: AMLs are benign tumors common in patients with TSC, associated with high morbidity (aneurysm, hemorrhage, chronic kidney disease), and can result in death.  Complication risk may correlate with increased AML volume.  Historically, AMLs were treated surgically with embolization or tissue-sparing resection.  In the EXIST-2 trial, everolimus significantly reduced AML volume in TSC patients.  This analysis estimates the cost of reimbursing everolimus for TSC-related AML to the UK healthcare system.  METHODS: A Markov model was built to analyze budget impact over five years.  The treated population is estimated using TSC and AML prevalence.  Adult patients with growing AML ≥3 cm are assumed eligible for everolimus.   Treatment reference costs are from the UK, resource utilization data from the Netherlands, efficacy and safety assumptions from EXIST-2.  The model assumed one-year treatment duration.  Responding patients (≥30% AML volume reduction) may restart everolimus upon AML regrowth.  Costs are discounted at 3.5% per annum. Sensitivity analyses were conducted.  RESULTS:  Up to 1,474 adults in the UK have TSC-related AML; 30% are assumed eligible for everolimus.  On average, 165 patients are estimated to be treated annually with everolimus (Year 1: 88; Year 5: 233) at an average cost of £4,600,000 (Year 1: £2,700,000; Year 5: £6,200,000).  Over five years, AML-related medical spending decreased £54,000.  Annual per patient treatment cost with everolimus is £31,000.  Results were most sensitive to patient prevalence, percent eligible for everolimus, and the percent experiencing ≥30% AML volume reduction.  CONCLUSIONS:  TSC is a relatively rare genetic disease for which everolimus is the only non-surgical treatment that has demonstrated efficacy in reducing AML volume.  Reducing AML volume may prevent long-term complications and avoid surgeries, resulting in decreased AML-related medical costs.  Further long-term studies are needed to better understand the benefits of everolimus in preventing AML-related morbidity and the associated costs.