Purpose/Objective(s): Our institution has used 3-dimensional conformal radiation therapy (3DCRT) to deliver whole breast irradiation (WBI) in the prone position since 1998 in order to address technical difficulties associated with treating large, pendulous breasts and/or large body habitus, and/or in patients with left-sided cancers to decrease radiation received by the heart. The goal of this study was to review our updated experience using prone breast WBI to determine whether the recurrence rates and survival patterns are acceptable in this set of patients. Materials/Methods: From 1998-2013, 397 women treated with breast conserving surgery underwent WBI in the prone position using 3DCRT. Patients were treated with a median of 50 Gy to the breast volume +/a boost of 10 Gy to the lumpectomy planning target volume. All patients had >12 month follow-up. Results: Median follow-up was 43.6 mo. The median age was 59 (27-91); 67% were post-menopausal. Median BMI was 32.4 (18.6-64.6). Tumors were Tis-19.8%, T1-61.5%, T2-17.2%, T3-1.5%, and 3.3% had positive axillary nodes. Eight (2%) patients were diagnosed with an ipsilateral breast tumor (5-yr recurrence rateZ1.9%). Mean time to recurrence was 57.5 mo (19-127 mo). The original tumors were DCIS (2), infiltrating lobular (3), and invasive ductal (3). Focal DCIS margin was <2mm in 3 patients. The original tumor location and location of recurrence respectively was: lower outer quadrant (LOQ)-failed in UOQ, UIQ-failed in UIQ (2), central-failed central, UOQ-failed UOQ, LOQ-failed LOQ, UOQfailed LIQ, and UOQ-failed in skin and with distant metastases. Ipsilateral disease free survival was 97.6% at 5 yr. Distant metastasis free survival was 98.4% at 5 yr. Overall survival was 95.5% at 5 yr. Conclusion: In patients with large pendulous breasts, increased BMI and/ or left-sided tumors, delivering WBI in the prone position using 3DCRT results in recurrence rates and failure patterns similar to those anticipated using supine WBI. This series adds to the growing literature demonstrating prone WBI provides local control rates comparable to supine WBI with minimal toxicity to organs at risk. Author Disclosure: H. Saeed: None. H. Cheng: None. T.R. Kelly: None. J.A. Bovi: None. J.R. White: None. C. Bergom: None. A.D. Currey: None. J. Wilson: None.