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As many as 40 % of breast cancer patients undergoing axillary lymph node dissection (ALND) and radiotherapy develop lymphedema. We report our experience performing lymphatic–venous anastomosis using the lymphatic microsurgical preventive healing approach (LYMPHA) at the time of ALND. This technique was described by Boccardo, Campisi in 2009. LYMPHA was offered to node-positive women with breast cancer requiring ALND. Afferent lymphatic vessels, identified by injection of blue dye in the ipsilateral arm, were sutured into a branch of the axillary vein distal to a competent valve. Follow-up was with pre- and postoperative lymphoscintigraphy, arm measurements, and (L-Dex®) bioimpedance spectroscopy. Over 26 months, 37 women underwent attempted LYMPHA, with successful completion in 27. Unsuccessful attempts were due to lack of a suitable vein (n = 3) and lymphatic (n = 5) or extensive axillary disease (n = 1). There were no LYMPHA-related complications. Mean follow-up time was 6 months (range 3–24 months). Among completed patients, 10 (37 %) had a body mass index of ≥30 kg/m2 (mean 27.9 ± 6.8 kg/m2, range 17.4–47.6 kg/m2), and 17 (63 %) received axillary radiotherapy. Excluding two patients with preoperative lymphedema and those with less than 3-month follow-up, the lymphedema rate was 3 (12.5 %) of 24 in successfully completed and 4 (50 %) of 8 in unsuccessfully treated patients. Our transient lymphedema rate in this high-risk cohort of patients was 12.5 %. Early data show that LYMPHA is feasible, safe, and effective for the primary prevention of breast cancer-related lymphedema.