Introduction Lymphedema is one of the most serious complications following breast cancer treatment. While many risk factors are well described the role of seroma formation has recently produced mixed results. Therefore, we aimed to evaluate if seroma is a risk factor for development of lymphedema in one of the largest retrospective cohort studies. Material and methods We included all patients with unilateral breast cancer treated in the period of 2008-2014. Data regarding treatment and breast cancer characteristics were retrieved from the national breast cancer registry. Data regarding lymphedema treatment and seroma aspirations were retrieved from local treatment codes. Results In total 1822 patients were included of which 291 developed lymphedema. Multivariate cox regression analysis showed that seroma was an independent risk factor (HR 1.92 CI 1.30-2.85, p= 0.001). Other independent risk factors were lymphadenectomy, radiation therapy, chemotherapy, BMI above 30, total lymph nodes removed above 15 and higher number of metastatic lymph nodes. Conclusions Postoperative seroma doubles the risk of developing lymphedema. Future studies should examine if seroma reducing measures will lead to lower risk of lymphedema.