Clinical outcome of patients with oral cavity squamous cell carcinoma (OSCC) and contralateral neck recurrence (CLNR) remains poor. We sought to identify factors associated with CLNR and incorporate them into a risk stratification scheme. Between January 1996 and June 2006, a total of 913 consecutive OSCC patients treated by radical surgery were investigated. Postoperative adjuvant therapy was performed in the presence of pathological risk factors. The duration of follow-up was at least 24 months in all surviving patients. Outcome measures were the 5-year CLNR and overall survival rates. In the entire study cohort, the 5-year CLNR rate was 7% (55/913). Specifically, it was 18% (17/132) in patients with local recurrence (LR), and 5% (38/781) in those without (P = 0.0002). In multivariate analysis, extracapsular spread (ECS) was the only independent risk factor for CLNR in patients with LR. Tumor subsite, poor differentiation, and presence of pN + disease were significant predictors of CLNR in patients without LR. We identified two groups of patients with high CLNR rates. The first group consisted of patients with ECS at the initial diagnosis and LR. The second group consisted of subjects with tongue cancer without LR harboring at least two risk factors. We conclude that, in patients who achieved local control, postoperative contralateral neck treatment is recommended for subjects with tongue cancer and at least two risk factors. Once LR occurs, contralateral neck treatment is recommended in patients with ECS.