Background Residual fibroglandular breast tissue (RFGT) following a mastectomy is associated with the remaining of occult breast cancer at the time of mastectomy as well as an increased local recurrence risk thereafter. Despite its oncologic implications, data on measures to prevent RFGT are lacking. Therefore, in a first step knowledge of risk factors for RFGT is of uttermost importance in order to allow identification of patients at risk and subsequently adaption of the surgical treatment and potentially prevention of RFGT a priori. Methods We performed a systematic literature review in PubMed using the MESH terms residual fibroglandular breast tissue, residual breast tissue, mastectomy and risk factor followed by a retrospective data analysis including all patients with a mastectomy treated at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Austria, between 01.01.2015 and 26.02.2020 in order to identify risk factors of RFGT following a mastectomy. The primary aim of the study was to assess a potential difference in RFGT volume between the different types of mastectomy. The secondary objectives of the study were to identify other potential risk factors for RFGT as well as to compare the skin and subcutaneous fat tissue thickness pre- to postoperatively. Results Significantly higher RFGT volumes were observed following a nipple-sparing mastectomy (NSM) compared to a skin-sparing mastectomy (SSM) and radical mastectomy (RME) (p < .001). Furthermore, RFGT volume was significantly associated with the variables: reconstruction (p = .012), acellular dermal matrix (ADM) or mesh (p = .031), patient age (p = .022), preoperative fibroglandular tissue (FGT) volume (p = .012) and preoperative whole breast volume (including the skin envelope and nipple-areola-complex) (p = .030). The reduction in the postoperative compared to preoperative skin envelope thickness measured medially and laterally reached statistical significance in the NSM-cohort (medial p < .001, lateral p = .001) and showed a numerical difference in the RME and SSM-cohort. Conclusion Mastectomy type, reconstruction, ADM or mesh, patient age, preoperative FGT volume and whole breast volume were identified as risk factors for RFGT in univariable analysis. The observed reduction in the post- compared to preoperative skin envelope thickness should be avoided considering the known associated increase in risk for ischemic complications. Keywords: Residual fibroglandular breast tissue, Mastectomy, Risk factor, Nipple-sparing mastectomy