Purpose: To examine the feasibility and acute toxicities of an accelerated, partial breast, intensity-modulated radiotherapy (IMRT) protocol. Methods and Materials: Between February 2004 and August 2005, 55 patients with Stage I breast cancer and initial follow-up were enrolled at four facilities on a HealthONE and Western institutional review board–approved accelerated partial breast IMRT protocol. All patients were treated in 10 equal fractions delivered twice daily within 5 consecutive days. The first 7 patients were treated to 34 Gy, and the remaining 48 patients were treated to 38.5 Gy. Results: The median follow-up after IMRT was 10 months (range, <1–19) and after diagnosis was 11.5 months (range, 2–21). No local or distant recurrences developed. The T stage distribution was as follows: T1a in 11 patients, T1b in 24, and T1c in 20. The median tumor size was 9 mm (range, 1–20 mm). Breast cosmesis was judged by the patient as poor by 2, good by 12, and excellent by 40 (1 patient was legally blind) and by the physician as poor for 1, good for 10, and excellent for 44 patients. Breast pain, as judged by patient, was none in 34, mild in 19, moderate in 2, and severe in 0 patients. There was a single report of telangiectasia but no incidents of significant edema. Compared with historic controls for whom three-dimensional treatment planning techniques were used, IMRT provided similar dose delivery to the target while reducing the volume of normal breast included in the 100%, 75%, and 50% isodose lines. Conclusion: This initial report prospectively explored the feasibility of accelerated partial breast IMRT. After short-term follow-up, the dose delivery and clinical outcomes were very acceptable. We believe this regimen deserves additional investigation under institutional review board guidance. [Copyright &y& Elsevier]