Objective: The primary objective was to evaluate seroma formation in a comparison between the lymphatic ligation technique and conventional axillary lymph node dissection. The secondary objective was to evaluate the factors affecting seroma formation. Materials and Methods: A randomized control trial was conducted between January 2014 and November 2017. 68 consecutive patients undergoing mastectomy with axillary lymph node dissection by one experienced surgeon. The patients were randomly sampled and assigned to Group 1 (lymphatic ligation; n=34) and Group 2 (conventional surgery; n=35). Results: 18 patients had developed seroma (26.09%) with 8 (23.53%) patients who were in the lymphatic ligation group and 10 (28.57%) patients who were in the conventional group. No statistical significance was discovered in seroma formation (P=.633), drain duration (P=.238) or total drain volume (P=.330) between the two groups. Longer operative time was statistically and significantly correlated with lymphatic ligation (P=.002). Age, BMI, total drain volume, and drain dislodgement were significant factors influencing seroma formation (P=.005, P=.002, P=.008, P=.015, respectively). Multivariate analysis showed age and BMI were significant factors influencing seroma formation (P=.008, P=.025, respectively). Conclusion: The lymphatic ligation technique could not reduce the incidence of seroma formation. Age, BMI were the factors influencing seroma formation in the patients undergoing mastectomy with axillary lymph node dissection.