© Mary Ann Liebert, Inc. 2014. Background: Factors associated with lymphedema development after breast cancer surgery are not well established. The purpose is to assess the value of patient, disease and treatment-related factors predicting lymphedema development. Methods and Results: This study included 371 women with primary invasive breast cancer treated surgically between 2005 and 2009 with follow-up until December 2011. At each follow-up visit, both upper limb circumferences were measured at seven points to calculate the upper limb volume. Kaplan-Meier and Cox regression models for survival were applied. By the end of the follow-up period, 33.4% of women (n=124) had developed lymphedema. According to volume, lymphedema at diagnosis was mild in 78.5%, moderate in 19.0%, and severe in 2.5% of them. A 77.4% of lymphedema had enough clinical relevance to be treated. The probability of developing lymphedema within 12, 24, and 36 months post-surgery was 28.7% (95%CI 24.1-34.0%), 34.6% (95%CI 29.5-40.2%), and 38.3% (95%CI 32.8-44.3%), respectively. High stages, axillary lymph node dissection, chemotherapy, radiotherapy, and postoperative seroma were predictors of lymphedema in the bivariate survival analysis. Only axillary lymph node dissection and radiotherapy maintained their significance in the multivariate model. When the analysis was restricted to patients who underwent axillary lymph node dissection, the number of nodes excised did not influence the occurrence of lymphedema. Conclusions: Axillary lymph node dissection and radiotherapy affected lymphedema development. This study provides support that breast cancer patients with such characteristics should be closely monitored, especially during the first year after surgery.