128 Background: Traditional fractionation for whole breast radiation therapy after breast-conserving surgery has been 50Gy in 25 fractions over a 5-week period, with or without a 10 Gy boost. Hypofractionation has recently been adapted for early-stage invasive breast cancer, typically treating with 42.5 Gy in 16 daily fractions. This approach has been shown to have equivalent efficacy as the more traditional schedule. Its application to patients with DCIS has been an extrapolation of these data, and warrants further examination. This retrospective analysis reviews toxicity outcomes in women with DCIS treated with hypofractionation at our institution. Methods: 59 women with DCIS treated with lumpectomy and hypofractionated radiotherapy with or without boost between 2006 and 2010 at the Einstein-Montefiore Cancer Center were identified. Median age was 65 (39-85). Median follow-up was 13.7 months (2–37.6). Surgical margin status was negative in 55, positive in 1, and unknown in 3. Thirteen patients had high-grade DCIS, 17 intermediate-grade, and 13 low-grade nuclear features, and 16 did not have grade delineation. 68% of patients (40 women) had disease that was positive both for ER and PR receptors, 2 women were simultaneously positive for ER and PR, 5 women had ER-only positive disease, 2 women had HER2-neu-only positive disease, 1 woman was positive for both ER and HER2-neu receptors, 1 woman was positive only for PR receptors, and 6 women were negative for all receptors; receptor status of specimens from 2 patients is not known. All women were treated with whole-breast hypofractionated therapy (42.4 Gy, in 16 fractions of 2.65 Gy each). 49 women received a boost to the lumpectomy cavity consisting of 10Gy in 5 fractions or 9.6 Gy in 4 fractions at the physician’s discretion. Results: With this regimen, no patient experienced acute RTOG grade 3 or higher skin, or other toxicity. No treatment breaks were required due to toxicity. The most common side effects were grade 1 dermatitis, followed by grade 2 dermatitis with mild edema of the treated breast. Conclusions: Our results suggest that postoperative hypofractionated radiation to the breast is well tolerated by women with DCIS and does not result in untoward acute toxicity.