<h3>Purpose/Objective(s)</h3> There is limited published data on definitive chemoradiation therapy for vulvar cancer. A retrospective multi-institutional cohort study was conducted to determine the efficacy, patterns of failure and long-term toxicity of high-dose radiation therapy (RT) for the primary treatment of vulvar carcinoma. <h3>Materials/Methods</h3> DRIVE (definitive radiation therapy for primary vulvar cancer) is a multicenter cohort study evaluating outcome for definitive high-dose conformal RT (dRT) for first line treatment of vulvar cancer. Treatment compliance, toxicity and patterns of failure were investigated. Actuarial locoregional control (LRC) and survival (OS) were estimated using Kaplan-Meier method and compared using log rank test. Herein, we present our preliminary results. <h3>Results</h3> In total, 48 patients [median (interquartile range) age, 57 (46-67) years] who received dRT between 2010 and 2020 were analyzed. Median follow-up was 28 (2–113) months. Cohort included 15 (31%) with stage I-II, and 33 (69%) patients with stage III-IV disease. Inguinal nodes alone were involved in 13 patients (27%); 19 (40%) had inguinal and/or pelvic node metastases. Elective surgical staging of groins was performed in 16 (33%) patients, of whom 7 had involved nodes. Intensity-modulated RT (IMRT) was used in 45 (94%) patients, and 3 (6%) received 3D-conformal RT. Median tumor dose was 64Gy (52-74.8Gy). Concurrent platinum-based chemotherapy was administered in 40 (83%) patients (1-8 cycles). Clinical complete response (CR) was achieved in 81.3% (39/48) patients at the primary site, and 84% (27/32) at involved nodes. Eight (16.7%) patients had persistent/recurrent disease following treatment, all within treatment volume; 5 (10%) patients developed distant metastasis. Actuarial 2 and 5-year LRC was 77.7% and 73%, respectively. Two and 5-year overall survival were 71% and 55%, respectively. On univariate analysis, determinants of inferior LRC were stage III/IV (p=0.04), non-IMRT technique (p=0.05) and <2 cycles of chemo (p=0.03). Treatment compliance included 90% (43 patients) completing planned treatment, 11/48 (23%) hospitalization, 6/48 (12.5%) blood transfusion, 12/48 (25%) with >5 days interruptions and median weight loss of 2.6Kg during RT. Of 40 evaluable patients, 25 (63%) developed significant vaginal stenosis. Vulvar necrosis was observed in 5 (10%) patients, all received ≥64Gy [2 treated with hyperbaric oxygen, 1 had musculocutaneous flap-reconstruction]. No acute/chronic grade 3 GI or GU toxicity, or any grade 5 toxicities were seen. <h3>Conclusion</h3> Definitive high-dose RT for vulvar cancer achieves high rates of local control, good compliance with acceptable dose dependent long-term toxicity. Use of IMRT does not result in increased geographic miss and was associated with improved locoregional control over existing prospective data from GOG 205 study.