BACKGROUND: Cell-assisted lipotransfer (CAL), a technique of autologous adipose transplantation enriched with adipose-derived stem cells (ADSCs), has the potential to improve cosmetic outcomes at irradiated sites. However, many concerns have been raised about the possibility of ADSCs increasing oncological risk in cancer patients. With the increasing demand for CAL reconstruction, there is an urgent need to determine whether CAL treatment could compromise oncological safety after radiotherapy, as well as to evaluate its efficacy in guiding clinical decisions. METHODS: A PRISMA-compliant systematic review of the safety and efficacy of CAL in breast cancer patients after radiotherapy was conducted. The PubMed, Ovid, Cochrane Library, and ClinicalTrials.gov databases were comprehensively searched from inception to 31 December 2021. RESULTS: The search initially yielded 1185 unique studies. Ultimately, seven studies were eligible. Based on the limited outcome evidence, CAL did not increase recurrence risk in breast cancer patients but presented aesthetic improvement and higher volumetric persistence in a long-term follow-up. Although breast reconstruction with CAL also had oncological safety after radiotherapy, these patients needed more adipose tissue and had relatively lower fat graft retention than the non-irradiated patients (P < 0.05). CONCLUSIONS: CAL has oncological safety and does not increase recurrence risk in irradiated patients. Since CAL doubles the amount of adipose required without significantly improving volumetric persistence, clinical decisions for irradiated patients should be made more cautiously to account for the potential costs and aesthetic outcomes. There is limited evidence at present; thus, higher-quality, evidence-based studies are required to establish a consensus on breast reconstruction with CAL after radiotherapy.