Heavier women and/or those with large, pendulous breasts have documented higher rates of severe acute and late toxicity and poorer cosmetic outcomes from whole breast irradiation (WBI) after lumpectomy for breast conservation. Using contour based 3-D treatment planning in the prone position for breast irradiation this institution sought to improve these outcomes. Between 1999 - 2005, 83 women received breast irradiation in the prone position due to large pendulous breasts and/or their, body habitus - 78 have > 1 year follow-up. All patients underwent CT planning in the prone position. Target breast volume (TBV), lumpectomy volume, ipsilateral lung and heart (left sided) were contoured for each case. Treatment goals were: 95% of the TBV minimally receive 90% of the dose prescribed to isocenter for the WBI, and 95% of the lumpectomy volume received 100% of the final prescribed dose. WBI was delivered with a mean dose of 49 Gy using an average of 3 beams. Mixed beam energy was used for 76%. A boost was given to 78% (10 Gy over 5 fractions with photons for 95%). Acute and late toxicity were scored according to the Common Toxicity Criteria Version 3.0. Cosmetic outcome is assessed by the Harvard Scale. Analyses were done assessing the influence of BMI and TBV on rates of Grade 2- 3 toxicities of dermatitis, breast pain, fibrosis and fair-poor cosmesis. The patient population was an average 63′ tall (58–71) and 201 lbs(114–322), corresponding to a BMI of 35 (22–51). The mean TBV was 1579cc (345–4800). Mean age at diagnosis was 61, and 77 % were postmenopausal. The tumors were Tis 16%, T-1 65%, T-2 16%, T-3 2%, and 14 % had positive axillary nodes. Chemotherapy was delivered to 33% prior to RT. The median follow-up is 26 months. Acute toxicity was as follows: Dermatitis- Grade (G) I 27%, G- II 68%, G- III 5 %. Breast edema - G- I 14%, G-II 1% G-III 1%. Breast pain - G- I 42%, G-II 25%, G- III 0% .Fatigue - G-I 68%, G-II 1%, G-III 0%. Moist desquamation developed in 15% and was confined to infra-mammary folds in 14% of these. For late toxicity: hyper pigmentation G-I 29%, telangiectasias 5% and fibrosis which was G-I 44%, G-II in 5%. Nipple/ areola deformity and volume loss leading to asymmetry was seen in a total of 11% and 25% patients respectively. Overall 6% experienced grade II or greater late toxicity. The cosmetic result was good or excellent in 85%, fair in 8% and poor in 1%. BMI was associate with both breast pain and cosmesis as follows: Grade 2–3 breast pain was 42% in those with a BMI >36, 19% for a BMI 33–35, and 17% for a BMI <32 (p=0.038). A fair-poor cosmesis was seen in 20% of patients with a BMI >36, 8% for a BMI 33–35-%, and 0% for a BMI <32 (p=0.024). There was no effect of BMI on higher rates of dermatitis and TBV size was not associated with higher rates of grade 2–3 toxicity or poor-fair cosmesis. In this patient population of fuller stature breast cancer patients with large pendulous breast, the use of contour-based 3-DCRT in the prone position resulted in an acceptable rate of acute toxicity, a low rate of late toxicity, and a high rate of good- excellent cosmetic outcomes.