PURPOSE/OBJECTIVE: We present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines. MATERIALS/METHODS: We identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient's ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time. RESULTS: 237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 - 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%. CONCLUSION: There is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.