Objective: Mastectomy is still a rational option for many women with breast cancer. However, the extensive dissection will lead to a large dead space beneath the flap that hampers the adherence to the tissue bed, which increase the seroma rate. Including flap quilting, several surgical techniques have been used to obliterate the dead space. However, there are conflicting results in the effectiveness at reducing the incidence of seroma. This meta-analysis was conducted to better assess the role of the use of quilting in seroma formation after mastectomy. Data sources, methods of study selection: An extensive literature search was performed in the PubMed, Embase and Cochrane databases. Pooled Odds ratio (OR) with 95% confidence intervals (CI) was analyzed. Tabulation, integration and results: A total of 8 trials involving 984 patients were included. Flap quilting showed seroma rate benefit of 20.1% vs 38.4% (OR 0.24, 95% CI 0.10–0.59, p = 0.002). Conclusion: Quilting significantly decreased the seroma rate in patients with breast cancer undergone mastectomy, and flap quilting is a valuable option for patients.