Background: The addition of oxaliplatin to fluorouracil-based regimens in the adjuvant treatment of colorectal cancer (CRC) has been shown to improve overall survival at the expense of increased toxicity. Toxicity may be higher among older patients who may also derive less benefit from oxaliplatin. The incidence of toxicity in the elderly is unknown. Methods: A cohort of patients ≥ 66 years old diagnosed with Stage II and III CRC between 2007 and 2011 in Ontario, Canada was identified using the Ontario Cancer Registry. Linked administrative databases were used to identify patients treated with oxaliplatin who were subsequently diagnosed with peripheral neuropathy (PN) or received a new prescription for a neuropathic pain medication. Patients were stratified into two age strata, ages 66-69 and ages ≥ 70, and each group was compared to a control cohort receiving non-oxaliplatin-based adjuvant chemotherapy (AC). Cause-specific hazard models were used to estimate the effect of Oxaliplatin exposure on the cause-specific hazard of PN and associated neurotoxicity outcomes after accounting for the competing risk of death. Results: We identified 3,607 patients aged ≥ 66 with Stage II and III CRC, of whom 1,541 were treated with an oxaliplatin-based AC regimen. Compared to control subjects receiving non-oxaliplatin based AC, patients ≥ 70 years old treated with oxaliplatin were more likely to be diagnosed with PN (cause-specific hazard ratio (CHR) age ≥ 70, 2.07 [95% CI, 1.43-3.00; p < 0.001]) and receive a new prescription for a neuropathic pain medication (CHR age ≥ 70, 1.86 [95% CI, 1.43-2.42;p < 0.001]). In patients aged 66-69, oxaliplatin use was not associated with a new diagnosis of PN (p = 0.903), but was associated with an increased likelihood of receiving a prescription for a neuropathic pain medication (CHR age 66-70, 1.92 [95% CI, 1.22-3.03; p = 0.005]). By the end of one year, the cumulative incidence of PN was 3.21% (95% CI, 2.02-4.81) for ages 66-69 and 5.51% (95% CI, 4.14-7.15) for age ≥ 70. Conclusions: In this population-based cohort of CRC patients ≥ 70 years old, treatment with oxaliplatin is associated with a significant risk of developing PN and requiring treatment with neuropathic pain medications.