To investigate the incidence of the contralateral neck failure (cRF) rate and outcomes among patients with well-lateralized locally advanced oral cavity squamous cell carcinoma (OSCC) with/without ipsilateral or bilateral neck adjuvant irradiation. Total 149 patients with lateralized OSCC who have undergone curative surgery with pathologically proven pT3/4 or pN0-2b between 2007–2017 were retrospectively enrolled. Those with cross midline, neck-level 1a involvement, and positive extra-nodal

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... nsion (ENE) were excluded. The median follow-up time was 5.2 years (range, 2.91–7.83). Pathological stages T3 and T4 were 22.7% and 56.8%, respectively. Pathologically negative and positive lymph nodes were 61.4% and 38.6%, respectively. The cumulative incidence of 5-year cRF rate was 3.57% (95% CI, 1.3–7.7%). No significant differences in the 5-year CSS, LRRFS, DMFS, and cRRFS were observed among those undergoing unilateral and bilateral neck irradiation. Five patients (3.4%) had contralateral neck recurrence, all simultaneously with local recurrence. No isolated contralateral neck recurrence was identified. In conclusion, the cRF rate was acceptably low in patients with well-lateralized advanced OSCC with the initially uninvolved contralateral neck. Omitting contralateral neck irradiation with active surveillance could be safely considered without compromising the cure rate in such locally advanced OSCC patients.