Abstract Standard treatment after breast conserving surgery (BCS) has been whole breast irradiation (WBI), however, accelerated partial breast irradiation (APBI) has recently been shown to be an alternative in a select group of patients. APBI has been associated with early postoperative as well as delayed infections. In the current study, we compared rates of infectious complications between patients treated with catheter-based APBI and WBI. Patients were identified from a single-institution prospective registry from 2009 to 2011. Selection criteria included patients who underwent BCT with either single-entry APBI or WBI and fulfilled criteria for ABPI including ≥50 years, tumor size ≤ 3cm, pN0, and no lympho-vascular invasion. Data regarding treatment, patient comorbidities, and outcomes were obtained. Infectious complications were assessed from the date of APBI catheter insertion or from the date of surgery to start of WBI. Infectious complications were classified as early (≤ 30 days) or delayed (> 30 days). Fisher's exact test was used to compare the rate of infection between APBI and WBI. 91 patients were treated with single-entry catheter-based APBI and 267 patients were treated with WBI. Median follow-up time was 76.2 weeks for APBI patients and 115 weeks for WBI patients. Re-excision was required in 20 patients (21.7%) who underwent APBI and in 51 patients (19.1%) who underwent WBI. Overall, infection occurred in 13 patients (14.1%) who underwent APBI versus 39 patients (14.6%) who underwent WBI. In the APBI group, three (3.3%) patients had infection within 30 days and 10 (10.9%) had infection more than 30 days after catheter insertion. 24 (9.0%) patients had infections within 30 days after surgery and 15 (5.6%) patients occurred more than 30 days after surgery in the WBI group. Patients began WBI within an average of 84 days after surgery. In the APBI group, 4 patients required hospital admission, 5 patients had percutaneous aspiration, and one needed incision and drainage. 8 patients were managed with outpatient oral antibiotics. In the WBI group, 5 patients required hospital admission, 13 patients had percutaneous aspiration, and 30 patients were managed with outpatient oral antibiotics. Diabetes, smoking, and BMI >25 were factors commonly associated with infectious complications in both APBI and WBI but not statistically significant (P = 0.6, 0.09, 0.1. respectively). In contrast to other studies showing that patients treated with catheter-based APBI have higher rates of infection than patients treated with WBI, our study found no statistically significant difference in infection rates between the two groups. A majority of infections following APBI or WBI can be medically managed as an outpatient basis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-07.