Background: Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. Recent pathology reporting guidelines recommend stratifying ENE into minor (≤2mm) or major (>2mm) extent. Prior studies have suggested that the addition of chemotherapy to adjuvant radiation may not improve oncologic outcomes in minor ENE. We evaluated this through a large multi-institutional cohort study. Methods: Surgically resected primary T1-4,N1-N3,M0 OSCC with pathologic nodal disease treated between 2005-2018 from four institutions in three countries were included. Extent of ENE was re-classified by pathologists on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended as per standard guidelines, unless contraindicated. Uni- (UVA) and Multivariable analysis (MVA) assessed the effect of chemotherapy on survival and disease control in minor and major ENE subgroups. Outcomes were also assessed in propensity score matched cohorts for each subgroup. Results: A total of 764 patients were included, of whom 126 (16%) had minor ENE and 242 (32%) had major ENE. Adjuvant chemoradiotherapy was given in 51 (40.5%) with minor ENE and 115 (47.5%) with major ENE. On MVA, chemotherapy was not associated with improved overall survival (OS) (HR 0.97, 95% CI 0.55-1.73, p=0.92) for patients with minor ENE, however, there was significant OS benefit for patients with major ENE (HR 0.61, 95% CI 0.38-0.98, p=0.041) after adjusting for age, T-category, N-category, margin status, adjuvant radiation, LN ratio, LVI, PNI, and ECOG status. Patients with major ENE receiving adjuvant chemoradiotherapy had improved locoregional control (LRC) (HR 0.67, 95% CI 0.42-1.09, p=0.1) although this did not reach statistical significance. Propensity score matched analysis found that patients with minor ENE who did and did not receive chemotherapy had no difference in OS (52% vs. 52%, p=0.85), but those with major ENE did (44% vs 13%, p=0.008). Conclusions: In OSCC, the addition of chemotherapy to adjuvant treatment is beneficial in major ENE, but our group failed to demonstrate a benefit for minor ENE. The benefit of chemotherapy in major ENE may result from improved LRC. Minor ENE is a clinically relevant subgroup in OSCC that warrants distinctive adjuvant treatment considerations.