9557 Background: Lymphaticovenous anastomosis (LVA) is a physiologic surgery indicated for secondary lymphedema of the extremities, particularly for disease refractory to conservative management. Immediate lymphatic reconstruction (ILR) is prophylactic LVA concurrently performed with CLND. After the transected lymphatics are mapped through a dye injection, they are anastomosed to a nearby venous outflow tract. Though prophylactic LVA is increasingly being performed, its risk on cancer recurrence and distant metastasis is currently unknown. The purpose of this study was to compare the distant-metastasis free survival (DMFS) and relapse-free survival (RFS) times in melanoma patients who underwent prophylactic LVA during CLND versus those who underwent conventional CLND for grossly metastatic disease. Our study is the first prospective evaluation of the impact of prophylactic LVA on DMFS in patients undergoing CLND. Methods: This was a prospective study of patients with cutaneous melanoma who underwent CLND with concurrent LVA (LVA group) or CLND alone (comparison group) between 2012 and 2021. Patients were excluded if they had non-melanoma skin cancers, stage IV cancers before CLND, microscopic lymphatic disease only or follow-up time of less than 12 months who did not die from melanoma-related causes. The comparison group consisted of all consecutive patients that underwent CLND alone and met inclusion criteria. To reduce surgical technique variability, all cases were performed by a single, high-volume surgeon at a tertiary care center. Results: A total of 46 melanoma patients underwent prophylactic LVA during this time period. Twenty-three of these patients met all inclusion criteria and were included in the LVA group. Twenty-two consecutive patients that underwent CLND alone were included in the comparison group. All patients underwent either axillary or inguinal CLND. Average number of lymph nodes removed during CLND were 18.20 ± 9.61 and 17.04 ± 9.97 for the LVA and comparison groups, respectively (p = 0.69). Size of largest metastatic tumor in lymph nodes was 45.91 ± 35.03 mm and 44.54 ± 23.32 mm, respectively (p = 0.99). Average time to first recurrence diagnoses was 6.75 ± 3.54 months vs 8.28 ± 5.66 months. For distant metastases only, the average time to first recurrence diagnoses was 6.16 ± 3.79 months and 9.39 ± 6.19 months, respectively (p = 0.25). There was no significant difference in recurrence type between the two groups (p = 0.66). There were no differences in DMFS and RFS times between the LVA and comparison groups. Conclusions: Prophylactic LVA performed for grossly metastatic melanoma does not negatively impact DMFS nor RFS. Considering the extremely aggressive nature of melanoma, our finding is potentially applicable to other cancers that are amenable to CLND and LVA.