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Purpose: For selected early breast cancers, intraoperative radiation therapy (IORT) at the time of lumpectomy can be an efficient alternative to fractionated whole breast radiation therapy (WBRT). However, some patients are later recommended WBRT after IORT due to surgical pathologic findings. To understand risk factor identification rates triggering WBRT recommendation, we analyzed adverse prognostic features based on multiple international criteria for suitability for accelerated partial breast irradiation., Methods and Materials: We performed a single-institution retrospective review of all 200 nonrecurrent invasive breast carcinomas that received IORT in 20 Gy to the tumor cavity using a 50 kV photon applicator between January 2011 and December 2015. IORT eligibility was based on the 2009 accelerated partial breast irradiation Consensus Statement from the American Society for Radiation Oncology (ASTRO). IORT was offered as the sole radiation modality to patients meeting 0-1 "cautionary" and no "unsuitable" criteria before lumpectomy. WBRT was recommended after IORT when 2+ cautionary and/or 1+ unsuitable criteria were met after accounting for resection pathology. We recalculated WBRT recommendation rates using initial and reresection margins for ASTRO consensus, Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations, and TARGeted Intraoperative radioTherapy vs. Postoperative Radiotherapy trial "prepathology" stratum protocol., Results: Depending on the selection criteria chosen, rates of WBRT recommendation can vary from 4.5% to 33%., Conclusions: WBRT recommendation rates of 30-33% after lumpectomy and IORT are observed when the WBRT indication is a single ASTRO cautionary/unsuitable, Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology intermediate/high-risk criterion, or TARGeted Intraoperative radioTherapy vs. postoperative radiotherapy trial protocol recommendation. Alternatively, allowing for re-excision to clear margins and accepting one ASTRO cautionary factor lowered the rate of WBRT recommendation to 9.5%., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)