Drainage duration and seroma formation occurring after mastectomy with or without axillary surgery lengthens hospitalization and delays adjuvant treatment. The aim of the study was to evaluate the effect of quilting in the prevention of seroma after mastectomy for breast cancer.Eighty-two breast cancer patients about to undergo mastectomy with or without axillary surgery lymphadenectomy were enrolled in the study. We conducted an observational comparison between 41 patients in whom quilting with closed suction drainage was used and 41 patients in whom drainage only was used.The mean drained volume was significantly lower in the quilting group compared with the control group on days 1 and 2 (day 1: 107.1 mL vs. 156.5 mL; P = .02; day 2: 108.4 mL vs. 162.8 mL; P = .01). The mean drainage period was shorter in the quilting group (4.6 vs. 5.3 days; P = .046). There were fewer needle aspirations for seroma in the padding group (n = 14, 34.1% vs. n = 24, 58.5%; P = .03).The use of padding after mastectomy seems to reduce seroma formation, volume drained, and length of drainage time.