BackgroundTotal mastectomy and axillary dissection is a common procedure for breast cancer patients in our institution. Seroma is common. This study aimed to compare the quilting suture and conventional closure in prevention of seroma after total mastectomy and axillary dissection.MethodsThis randomized comparative study was carried out from January 2018 to June 2019 in Yangon General Hospital. One hundred and forty patients (70 conventional and 70 quilting) were included. For quilting group, customized strategically placed interrupted alternate sutures were placed 2–3 cm apart with 3/0 vicryl sutures between skin flap and pectoral muscle.ResultsAge, body mass index and tumour diameter were comparable between the groups. The mean duration of operation was 111.44 ± 7.045 min in conventional and 124.5 ± 6.39 min in quilting (P = 0.0001). The mean drain output for conventional group was not significantly different from quilting group. In quilting, some area developed dimpling which resolved within a week. A total of 21 (30%) patients in the conventional group and 10 patients (14.3%) in the quilting group developed seroma (P = 0.041). The mean frequency and amount of seroma aspiration were significantly lower in the quilting group. Shoulder movement limitation and analgesia use showed no significant difference.ConclusionAlthough total amount of drain output, duration of drain, hospital stay and post‐operative complications were not different, the incidence of seroma was significantly lower in quilting group. Seroma is treated with more ease in the quilting group as the frequency and amount of aspiration were lower and less frequent follow‐up visits were required. Quilting can reduce the seroma incidence in total mastectomy and axillary dissection for breast cancer patients.