187 Background: Increasing constraints on health care resources call for implementation of breast cancer treatment strategies that preserve treatment efficacy while reducing healthcare cost. In this investigation, we model potential cost savings associated with the use of single-fraction intraoperative radiotherapy (IORT) compared to two commonly used alternative radiotherapy approaches. Methods: A database survey was performed of female subjects undergoing breast conserving surgery (BCS) with or without sentinel lymphadenectomy at HealthCare Partners, a major IPA in metropolitan Los Angeles, CA. Subjects were identified by cross-referencing ICD-9 codes (174.0-174.9) for invasive breast cancer, CPT codes for BCS (19120, 19125, or 19301), and CPT codes for sentinel node biopsy without ALND (38500, 38525, or 38740). Calculations were based on the 2011 U.S. Medicare Fee Schedule. Treatment costs and savings were modeled assuming that patients with node-negative disease who underwent BCS were eligible for accelerated partial breast irradiation based on American Society of Breast Surgeons Guidelines (age ≥45, IDCA, DCIS, size ≤3 cm, node and margin negative). Results: A sample of 1,478 women meeting criteria was evaluated to determine the average per-patient cost of breast radiotherapy comparing three modalities: single-fraction IORT ($4,402), 5-day multi-lumen balloon brachytherapy (MLBB) (e.g., MammoSite) ($12,021), and standard 6-week whole breast external beam radiotherapy followed by a tumor bed boost (WBRT) ($8,988). IORT was approximately 49% the cost of standard 6-week WBRT and 37% the cost of MLBB. Conclusions: When eligible breast cancer patients are offered IORT as an alternative to WBRT, the expenditures from this sample may be reduced from $13.3M to $6.5M, a savings of $6.8M. Compared to MLBB, IORT may reduce radiotherapy expenditures from $17.8M to $6.5M, a savings of $11.3M. [Table: see text]