Despite the development of minimal access dissection techniques, use of superficial groin dissection alone, and other recommendations to reduce morbidity in melanoma treatment, the incidence of lymphedema is still significant. The purpose of the current study was to assess the efficacy of microsurgical methods to limit the morbidity of inguinal lymphadenectomy. We conducted a retrospective review of patients who underwent groin dissection for melanoma treatment from February 2006 to April 2009. A total of 59 melanoma patients with positive groin lymph nodes comprised 18 patients (T-group) with melanoma in the trunk and 41 patients (E-group) who had melanoma in an extremity and currently have lymphedema. The T-group patients underwent primary prevention of lymphedema with microsurgical lymphatic-venous anastomoses (LVA) performed simultaneously with groin dissection. The E-group patients underwent LVA to treat the secondary lymphedema after an accurate oncological and lymphological assessment. Limb volume measurements and lymphoscintigraphy were performed pre- and postoperatively to assess short and long term outcome. No lymphedema occurred after microsurgical primary preventive approach in the T- group. Significant (average 80% reduction of pre-op excess volume) reduction of lymphedema resulted after microsurgical treatment for secondary leg lymphedema. Post-operative lymphoscintigraphy in 35 patients demonstrated patency of microsurgical anastomoses in all cases with an average follow-up of 42 months. Study results demonstrate that microsurgical LVA primary prevention prevented lymphedema after inguinal lymphadenectomy in the T-group patients. In addition, lymphatic-venous multiple anastomoses proved to be a successful treatment for clinical lymphedema with particular success if treated at the early stages.