Seroma is a common complication following breast cancer surgery and the controllable predictive factors remain unknown. Patients who underwent mastectomy with axillary dissection between 2008 and 2011 in our hospital were retrospectively investigated. The demographics, clinical characteristics and therapeutic factors of each patient were recorded. The association of seroma incidence with each variable was evaluated by univariate logistic regression analysis. All the variables were considered independent predictors of seroma incidence. The probability of developing seroma following surgery was evaluated by multivariate logistic regression analysis. A total of 102 patients, with a mean age of 54.86 +/- 13.02 years (range, 30-89 years), were included in this study and the incidence of seroma was found to be 22.55%. The operative time (P=0.0066, coefficient =0.0261, OR=1.03) and the use of patient-controlled intravenous analgesia (PCA) (P=0.0002, coefficient =-1.8089, OR=0.03, ref=no) was significantly associated with the incidence of seroma postoperatively. In conclusion, the prediction of the development of seroma following mastectomy with axillary dissection is challenging. However, a longer operative time and the non-use of PCA may represent potential risk factors for this complication.