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To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) in preventing lymphedema (LE) in a prospective cohort of patients.LE is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 25%. LYMPHA has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure, however, requires microsurgical techniques and significant coordination between services.All patients, undergoing ALND with or without S-LYMPHA between January 2014 and December 2016 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect LE. The incidence of LE was compared between ALND with and without S-LYMPHA.A total of 380 patients were included in the analysis. Median follow-up time was 15 (1–32) months. Patients, who underwent S-LYMPHA, had a significantly lower rate of LE both in univariate and multivariate analysis [3% vs 19%; P = 0.001; odds ratio 0.12 (0.03–0.5)]. Excising more than 22 lymph nodes and a co-diagnosis of diabetes mellitus were also correlated with higher clinical LE rates on univariate analysis, but only excising more than 22 lymph nodes remained to be significant on multivariate analysis.S-LYMPHA is a simple method, which decreases incidence of LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.