Inflammatory breast cancer (IBC) has been characterized by high locoregional recurrence (LRR) rates even after trimodality therapy. We recently reported excellent locoregional control among patients treated since formally dedicating an IBC-specific clinic and research program in 2006. Institutionally, a standard twice-daily (BID) dose escalation regimen for all IBC patients was de-escalated in select cases in 2006 after review demonstrated young age, incomplete response to neoadjuvant therapy, and positive margins identified subsets with maximal benefit from dose escalation. Here we examine local control and toxicity rates with BID versus once daily (QD) approaches. We identified 103 non-metastatic IBC patients who received trimodality therapy at our institution from 2007-2015 in a prospectively-collected database. Descriptive statistics were used to describe the study cohort and retrospectively extracted rates of radiotherapy-associated toxicity. The actuarial rate of LRR-free survival was analyzed using the Kaplan-Meier method. The median follow-up is 3.6 years. The median age is 52 years. Fifty-seven patients (55.3%) presented with stage IIIB disease, and 46 patients (44.7%) presented with stage IIIC disease. Twenty-seven patients (26.2%) achieved breast pathologic complete response (pCR) and 38 (37.6%) cN+ patients achieved axillary lymph node pCR. Three patients (3.0%) had a close/positive surgical margin (<2.0 mm). Thirty-nine patients (37.9%) received post-mastectomy radiotherapy (PMRT) to the chest wall and undissected regional lymphatics in QD fractions (median dose 50.0 Gy/25 fx, median boost dose 10.0 Gy/5 fx) and 64 patients (62.1%) received BID PMRT (median dose 51.0 Gy/34 fx, median boost dose 15.0 Gy/10 fx). Per institutional practice, patients >45 years of age, pCR after neoadjuvant chemotherapy, and negative surgical margins were dispositioned to de-escalation with QD treatment. Crude toxicity by CTCAE v4.0 grade (where appropriate) for QD and BID treatment were:Abstract TU_2_3342; Table 1ToxicityQDBIDPDermatitis G1-235 (89.7%)62 (96.9%)0.20 G34 (10.3%)2 (3.1%) G40 (0.0%)0 (0.0%)Infection1 (2.6%)2 (3.1%)1.00Rib Fracture2 (5.1%)4 (6.3%)1.00Symptomatic Lymphedema (G2+)10 (25.6%)8 (12.5%)1.00Symptomatic Fibrosis (G2+)1 (2.6%)0 (0.0%)0.38Symptomatic Pneumonitis (G2+)1 (2.6%)5 (7.8%)0.40Brachial Plexopathy0 (0.0%)2 (3.1%)0.53 Open table in a new tab Two BID patients (3.1%) and zero QD patients (0.0%) experienced LRR (P =0.53). Three- and 5-year LRR-free survival were 95.1% and 100.0% for BID and QD patients, respectively (P =0.25). Tailoring radiotherapy to clinical risk factors was associated with excellent locoregional control. De-escalation of PMRT from BID to QD was not clearly associated with reduced toxicity compared to BID, although retrospective data collection may limit this comparison.