<h3>Purpose/Objective(s)</h3> To report final results of a clinical trial of APBI using intensity modulated radiotherapy (IMRT) to deliver 27 Gy in 5 daily fractions following breast conserving surgery (BCS) prospectively designed to assess the efficacy and cosmetic outcomes of a 1-week, APBI regimen among women with early breast cancer. <h3>Materials/Methods</h3> Women ≥ 50 years, with lymph node-negative, ER positive, HER-2 negative breast cancer or ductal carcinoma in situ (DCIS), ≤ 3cm diameter, following BCS with margins ≥ 2mm, and excellent or good baseline cosmesis received 27 Gy in 5 daily fractions to the seroma plus 1 cm CTV and 0.7 cm PTV margins. Clinical photographs, patient and provider cosmetic scores, breast fibrosis, telangiectasia and pain were collected prospectively, prior to RT and at 6 weeks, 1 and 2 years after RT. The primary endpoint was the proportion of women who retained Excellent or Good cosmesis at 2 years using the EORTC Cosmetic Rating System. Cosmetic failure was deterioration from Excellent or Good to Fair or Poor. A panel of 5 radiation oncologists independently assessed the cosmetic photographs. Secondary endpoints were rates and grades of breast fibrosis, telangiectasia, breast pain, ipsilateral breast tumor recurrence (IBRT), overall (OS), breast cancer-specific survival (BCSS) and subsequent mastectomy. Efficacy outcomes were assessed at clinic visits and by review of charts. ClinicalTrials.gov registration: NCT02681107. <h3>Results</h3> A total of 298 patients were treated between April 25, 2016, and October 31, 2019. At a median follow up of 48 months, the 4-year OS was 98.5% (95% CI 96.1% - 99.5%) and BCSS was 99.7% (95% CI 97.6% - 99.9%). The 4-year IBRT rate was 3.3% (95% CI 1.1% - 6.4%). There were 10 contralateral breast events for a 4-year rate of 3.9% (95% CI 2.2% - 6.9%). There were 10 ipsilateral and 6 contralateral mastectomies. Two patients died of unrelated causes prior to 2 years; 79 patients declined in-clinic attendance due to COVID or competing comorbidities and 217 women had 2-year cosmetic photographs and clinical assessments performed. Consensus of the photo-panel cosmesis at baseline was: Excellent: n=116 (53%), Good: n=102 (47%), Fair: n=1 (0.5%) and Poor: n=0. Consensus overall cosmesis at 2 years was: Excellent: n=141 (65%), Good: n=78 (35%), Fair: n=0 and Poor: n=0. Most patients had either improved (n=168; 77%) or no change (n=43; 20%) in cosmesis at 2-years. No patient had cosmetic failure but 6 (3%) had a change from Excellent to Good at 2 years. Most patients reported either no (79%) or mild (21%) pain, with no moderate or severe pain. Two patients (0.9%) had grade 2 fibrosis and 5 patients (2%) had visible telangiectasia that did not detract from overall cosmesis. <h3>Conclusion</h3> APBI using 27 Gy in 5 fractions using a conformal IMRT technique, achieved excellent 2-year cosmesis with minimal toxicity. The IBRT risk was comparable to the contralateral new breast cancer risk and to local recurrence rates of recently published early breast cancer trials.