Background: Patients with high-risk stage II colon cancer (CC) may benefit from adjuvant chemotherapy, but additional prognostic markers are needed for better treatment stratification. We investigated the prognostic value of tumour infiltrating lymphocytes (TILs) in a true population-based cohort of patients with stage II CC. Methods: A total of 573 patients were included, representing all patients operated for stage II colon cancer in Denmark in 2002. Tumour blocks representing the deepest invasive part of the primary tumour were used for analysis. CD3+ and CD8+ TILs at the invasive front were evaluated by immunohistochemistry on whole tumour sections. The invasive area was manually outlined, and Visiopharm Integrator System software was used for quantification. Data were dichotomized for comparison with clinical data. The prognostic value was investigated in Cox proportional hazard models for recurrence-free survival (RFS) and overall survival (OS). Results: Low CD3+ or CD8+ TILs were significantly associated with poor RFS and OS, (p = 0.0021 and p≤0.0009, respectively, log-rank test). In multiple Cox regression analysis low CD3+ and CD8+ TILs were associated with reduced RFS with hazard ratio (HR) 1.386 (95% CI 1.039-1.850), p = 0.026, and HR 1.394 (95% CI 1.029-1.890), p = 0.032, respectively, independent of age, T-stage, localization, perforation, and microsatellite instability (MSI). In the subgroups of patients with low CD3+ or CD8+ TILs, there were no differences in survival between patients with MSI and microsatellite stable tumours, (p = 0.821 and p = 0.907, respectively). Conclusions: Low CD3+ and CD8+ TILs in the invasive area are both related to inferior prognosis in patients with stage II CC, and we recommend either of these parameters to be considered as an additional high-risk factor.