BACKGROUND: Autologous fat grating has become increasingly popular as a breast reconstructive procedure. Nevertheless, preclinical studies show that fat transfer to a previous breast cancer site could activate latent cancer cells, creating a favourable environment for disease recurrence. A systematic review and meta-analysis was performed to investigate whether fat grafting increases the risk of locoregional recurrence in patients formerly treated for breast cancer. METHODS: Based on PRISMA guidelines, a systematic review searching for randomised clinical trials and matched cohorts on the topic was performed in the electronic databases Pubmed, Embase, Web of Science, and Cochrane. The date of the last search was July 20, 2021. The meta-analysis assessed the comparison of locoregional recurrence between groups. RESULTS: From a total of 558 publications, data from nine matched cohorts (1.6%) reporting on 4247 subjects (1590 and 2657 subjects, respectively, in lipofilling and control groups) were suitable for inclusion in the meta-analysis. Neither of the outcomes had a statistically significant difference for disease recurrence. For the primary outcome, comparing locoregional recurrence rates between groups, the incidence rate ratio was 0.92 (95% CI: 0.68-1.26; P = 0.620). CONCLUSION: The present meta-analysis, which comprises the outcomes of the individual studies with the best current evidence on the topic so far, strengthens the evidence favouring the oncologic safety of lipofilling for breast reconstruction.