5609 Background: Adjuvant radiation (RT) has been demonstrated to improve overall survival (OS) in vulvar cancer patients with 2+ positive lymph nodes, but its role in patients with one positive lymph node is uncertain. We report on the largest and longest study of survival in patients with and without radiation following surgery in patients with vulvar cancer. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified node-positive women with squamous cell carcinoma of the vulva treated with and without external beam radiation following surgery. The Kaplan-Meier approach, log-rank tests and Cox modeling assessed OS. Results: All results are listed as women without vs with adjuvant radiation. From 1988 – 2008, 420 patients received surgery alone vs 753 women who received adjuvant radiation. Patient characteristics were well balanced across cohorts, including tumors ≤ or > than 2 cm (p = 0.31), grade (p = 0.41), marital status (p = 0.20), provider type (p = 0.49), and AJCC stage (p = 0.35). Both groups also had similar incidence of biopsy of any kind (p = 0.40), lymph node dissection (p = 0.77), median number of nodes excised (p = 0.12), and type of surgery (p = 0.49). Median age (75 vs 70 y, p <0.01) and race (94% vs 89% white, p = 0.01) were adjusted using Cox regression. Median survivor follow-up was 45 m (range 0 - 236 m). Adjuvant radiation was associated with survival across all node-positive patients (22 vs 29 m, p <0.01), as well as in the subset of women with just one positive lymph node (37 vs 70 m, p <0.01) or 2+ positive lymph nodes (14 vs 18 m, p <0.01). On multivariable Cox regression, adjuvant radiation (95% CI 0.85 - 0.96), diameter (CI 1.28 - 2.01), marital status (CI 0.65 - 0.93), the number of positive nodes (CI 1.06 - 1.11), and the ratio of positive-to-excised nodes (CI 1.61 - 2.98) were all associated with survival (p <0.01 for each). Conclusions: The largest cohort study of node-positive squamous cell carcinoma of the vulva suggests adjuvant radiation is associated with OS.Studies have reported that adjuvant radiation may provide a survival benefit in women with 2+ positive lymph nodes. Our findings suggest patients with one positive lymph node also may benefit from adjuvant radiation.