Abstract Background The aim of this study was to compare conventional suture with prolonged timing of drainage with quilting suture on the formation of seroma at pectoral area after mastectomy (ME) with sentinel lymph node biopsy (SLN) or axillary lymph node dissection (ALND) for breast cancer. Methods Three hundred and eighty-eight consecutive breast cancer patients were retrospectively analyzed and categorized into three groups. Patients in group 1 were with quilting suture, group 2 with conventional suture and 13–15 days drainage in situ, and group 3 with conventional suture and 20–22 days drainage. The primary outcome was the incidence of grades 2 and 3 seroma at anterior pectoral area within 1 month postoperatively. Cox regression was used for analysis. Results The incidence of grades 2 and 3 seroma was comparable among groups (9.5% vs. 7.9% vs. 5.3%, p = 0.437), as well as late grades 2 and 3 seroma among groups (4.3% vs. 2.9% vs. 1.5%, p = 0.412). Old age, high body mass index, and hypertension were independent risk factors for grades 2 and 3 seroma. Conclusions Prolonged timing of drainage to 13–15 days in conventional suture was long enough to decrease the incidence of grades 2 and 3 seroma as lower as that in quilting suture group at pectoral area within 1 month after mastectomy.