BACKGROUND: Adjuvant capecitabine and oxaliplatin (CAPOX) is a standard treatment for resected colon cancer; however, in patients with moderate renal impairment, the incidence of CAPOX-related adverse events (AEs) and the rate of early discontinuation are higher than in patients with no or mild renal impairment. The aim of this retrospective study was to assess the impact of baseline renal function on the safety and discontinuation of adjuvant CAPOX therapy started with the standard dose of capecitabine in elderly patients with colon cancer. METHODS: Data from patients aged ≥65 years old who received CAPOX at the standard starting dose as adjuvant therapy for stage II/III colon cancer were collected and analyzed retrospectively. Patients were divided into two groups based on their renal function: CLcr-H (patients with a creatinine clearance [CLcr] ≥50 ml/min) and CLcr-L (CLcr <50 ml/min), and AEs and discontinuations were assessed. RESULTS: Overall, 189 patients were assessed (CLcr-H group = 137 and CLcr-L group = 52). No patients experienced grade 4 AEs. The incidence of grade 3 CAPOX-related AEs was higher in the CLcr-L group (42.3%) than in the CLcr-H group (31.3%). The proportion of patients who discontinued treatment within four cycles due to AEs was also higher in the CLcr-L group (21.1%) than in the CLcr-H group (2.9%). Multivariate analysis identified that CLcr <50 ml/min was the only significant risk factor for CAPOX therapy discontinuation due to AEs (P = 0.0008). CONCLUSIONS: This study demonstrates that the tolerability of adjuvant CAPOX therapy was decreased in elderly patients with impaired renal function. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry number UMIN000016446.