e12618 Background: Conservative mastectomy with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implants have been placed in a submuscolar (SM) plane beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of this study was to compare outcomes of SM vs PP IPBR after conservative mastectomy in patients with histologically proven breast cancer treated with neoadjuvant chemotherapy (NAC). Methods: In this retrospective observational study we analyzed two cohorts of patients that underwent mastectomy with IPBR after NAC in our Istitution from January 2018 to December 2021. Conservative mastectomy was performed in 155 of the 400 patients that underwent NAC during the study period. Patients were divided in 2 groups based on the positioning of implants: 60 SM versus 95 PP. Results: The two cohorts were similar for age (mean age 45 and 42 years in the SM and PP group respectively) and follow‐up (32 and 21 months, respectively). Mean operative time was 55 minutes shorter in the PP group (298 and 243 minutes in the SM and PP group). No significant differences were observed in overall major complication rates. Implant loss occurred was observed in 1.6% of patients (1/60) in the SM group and 1,05% of patients (1/95) in PP group. No differences were observed among the two groups in local or regional recurrence. Conclusions: Our preliminary experience, that represents one of the largest series of PP-IPBR after NAC at a single Institution documented in the Literature, seems to confirm that PP - IPBR after NAC is a safe, reliable and effective alternative to traditional SM - IPBR with excellent aesthetic and oncological outcomes; it is easy to perfom, reduces operative time and minimizes complications related to manipolation of PPM. However this promising results need to be confirmed in prospective trials with longer follow-up.