We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using the GammaPodTM stereotactic radiation system. Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity was graded using the NCI version 4.0 and RTOG/EORTC late radiation scale. From 3/2019-10/2021, 74 patients were treated respectively. Of these, 38 were treated to 40Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 24 months (mo), range (r) 3-39mo. Median age was 63 years (r 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. 45/46 invasive tumors were ER+. 60/74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 221 acute grade 1 toxicities, and 28 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (10), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 54 Grade 1 late toxicities, 4 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis (2), and pain (2). Two patients developed grade 1 asymptomatic nonpalpable fat necrosis both diagnosed at 12 months after radiation treatments. The most common grade 1 late toxicities were breast pain (14), hyperpigmentation (8), fibrosis (10), and fatigue (5). Physicians scored cosmesis excellent or good 70/73 (95.8%), 58/60 (96.7%), 36/36 (100%),17/17(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 62/71 (83.7%), 53/59 (89.8%), 33/36 (91.6%), 17/18 (94.4%). There have been no reports of disease recurrences. Results at 24-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Continued analysis of all cohorts is in progress. gov identifier is NCT03581136.