Balloon catheter-based accelerated partial breast irradiation (APBI) may result in desirable short-term outcomes in patients undergoing breast conserving surgery. Prospective consecutive case series. Tertiary multidisciplinary referral center. Forty selected patients with invasive breast carcinoma undergoing breast conserving surgery and MammoSite device placement. Breast conserving surgery, sentinel and/or axillary node dissection, placement of the new balloon catheter applicator (MammoSite device), and APBI. Infection, early and late seroma, device explantation, time to initiating APBI, acute toxic effects on the skin, and cosmesis using the Harvard Scale. Thirty-nine patients underwent MammoSite device placement at the time of lumpectomy; 1 patient underwent percutaneous device placement after lumpectomy. Nineteen patients (49%) had drainage catheters placed in the breast cavity at the time of lumpectomy. Wound infection developed in 3 patients (8%). Five devices (12%) were explanted because of unfavorable final pathological findings or infection. The mean time to the start of APBI in patients who did not undergo simultaneous drain placement was 7.2 days (range, 5-12 days), compared with 5.1 days (range, 3-8 days) in patients who did (P = .008). With a mean follow-up of 13.3 months (range, 2-28 months), patients completing APBI had limited toxic effects on the skin, with excellent or good cosmetic results in 39 patients (97%). Use of the MammoSite system in APBI has favorable short-term outcomes. Infection and radiation treatment delay are common and may warrant use of perioperative antibiotics and drain placement, respectively. A small number of patients who have device placement at the time of lumpectomy will require explantation because of unfavorable final pathological findings. Short-term outcomes of MammoSite brachytherapy support further studies comparing APBI with standard whole breast irradiation in patients undergoing breast conserving surgery.