Abstract The indication for postmastectomy radiotherapy (PMRT) is mainly based on tumor stage and the extent of lymph node involvement. The results of EBCTCG meta-analysis (EBCTCG Lancet, 2014) support the need of radiation therapy (RT) for patients with one to three axillary metastatic lymph nodes (LN), as well as for patients with > 3 affected LN. In nearly 40% of patients with mastectomy (ME) RT is required. According to the plastic surgery statistics report 2020 approximately 80% of patients seeking breast reconstruction in the USA receive an implant-based breast reconstruction (IBBR), while 18% undergo autologous reconstruction (ASoPS 2020). PMRT, regardless of reconstructive method, has been found to have a detrimental effect on outcomes with increased postoperative complications and decreased patient satisfaction. Nevertheless, even in this cohort the number of breast reconstruction (BR) is increasing over time. Surgical techniques for ME and BR are advancing constantly. With the increasing use of skin-sparing ME (SPM) techniques, particularly nipple-sparing ME (NSM), one stage IBBR (single-stage direct-to-implant, DTI) become more popular. With the availability of supportive materials such as synthetic/biological mesh or acellular dermal matrix (ADM) there has been a significant improvement in pre-pectoral implant reconstruction. The impact of PMRT on the outcomes of pre-pectoral IBRR has been recently summarized in a systemic review and meta-analysis by Awadeen (Aesth Plast Surg, 2022). Wound infection, capsular contraction and implant loss were significantly more frequent in the irradiated than in the non-irradiated breasts. Several studies describe the delayed/2-stage IBBR in the setting of PMRT as more promising and discuss different timings of exchange from expanders to implant. In one systematic review, PMRT to permanent implants reduced the rate of reconstructive failure compared to TE (J Surg Oncol,2015). After prosthetic-based BR and RT, conversion to autologous reconstruction can always be considered. Recommendations for immediate autologous reconstruction vary when PMRT is required. PMRT can result in wound complications, fat necrosis and volume loss, but overall cosmetic results are better than with IBBR and PMRT. When undergoing delayed reconstruction after PMRT, the optimal time from PMRT to reconstruction is unknown. In patients with a history of RT, NCCN-guidelines (V.4.2022) recommend autologous reconstruction as the preferred reconstruction option. Fat grafting, which can optimize tissue perfusion and wound healing, is playing an emerging role in breast surgery. Lipofilling can be used to improve the thickness of the mastectomy flap and to recontour breast defects after PMRT. There is an increasing awareness for better understanding of the different reconstruction types to define target volumes depending on the varying risk for residual tissue and potential recurrences. The ESTRO-ACROP guidelines discuss adapted dose distribution in accordance with the different locations of the implant (pre-or sub-pectoral) (Radiotherapy and Oncology, 2019). The risks and benefits of immediate versus delayed as well as implant-based versus autologous reconstruction must be considered for each individual patient and should be planned in a multidisciplinary setting, especially when PMRT is required. Citation Format: Christine Solbach. How to reconcile novel reconstructive techniques with the need to radiate [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED6-3.