PURPOSE: To report acute toxicities in breast cancer (BC) patients (pts) recruited in a prospective trial and treated with accelerated partial-breast irradiation (APBI) using Volumetric Modulated Arc Therapy (VMAT) delivered with a hypofractionated schedule. METHODS: From March 2014 to June 2019, pts with early-stage BC (Stage I), who underwent breast conservative surgery (BCS), were recruited in a prospective study started at the National Cancer Institute of Milan. Pts received APBI with a hypofractionated schedule of 30 Gy in five daily fractions. Radiotherapy treatment (RT) was delivered using VMAT. Acute toxicity was assessed according to RTOG/EORTC criteria at the end of RT. RESULTS: Between March 2014 and June 2019, 151 pts were enrolled in this study. 79 Pts had right-side and 72 had left-side breast cancer. Median age was 69 (range 43-92). All pts presented with pathological stage IA BC, molecular classification was Luminal A in 128/151 (85 and Luminal B in 23/151 (15 cases. Acute toxicity, assessed at the end of RT, consisted of G1 erythema in 37/151 (24. 5 pts and skin toxicities higher than G1, did not occur. Fibrosis G1 and G2 were reported in 41/151 (27. 1 pts and in 2/151 pts (1. 3, respectively. Edema G1 occurred in 8/151 (5. 3 pts and asthenia G1 occurred in 1/151 (0. 6 pts. CONCLUSIONS: APBI with VMAT proved to be feasible and can be a valid alternative treatment option after BCS in selected early breast cancer pts according to ASTRO guidelines. A longer follow-up is needed to assess late toxicity.