The latissimus dorsi flap has been widely used in breast reconstruction surgery. Despite its potential advantages such as low donor morbidity and vascular reliability, the complication of donor-site seroma formation frequently occurs. Consecutive 174 patients who underwent breast reconstruction with the latissimus dorsi flap from 2001 to 2006 were retrospectively reviewed. The age, body mass index (BMI), smoking history, timing of reconstruction, type of breast surgery and nodal dissection, and several other intraoperative data were analyzed. The overall incidence of postoperative seroma was 21%. Increased age (>50 years) and obesity (BMI >23 kg/m2) were significant risk factors for seroma formation (P = 0.02 and 0.004, respectively). The patients who underwent skin-sparing mastectomy or modified radical mastectomy had higher incidence of seroma formation (28% and 33%, respectively) as compared with those who had breast-conservative surgery (11%). A significant correlation was found between the type of breast surgery and the incidence of seroma (P = 0.04). The type of nodal dissection did not affect the incidence of postoperative seroma (P = 0.66). We concluded that increased age, obesity, and invasive breast surgery are risk factors for donor-site seroma formation after breast reconstruction with the latissimus dorsi flap. Close attention should be paid to prevent development of postoperative seroma when operating on such high-risk patients.