Background: Oxaliplatin is commonly associated with acute neuropathy, as well as a more troublesome chronic neurotoxicity. Details regarding the clinical course of these toxicities are not well defined. Methods: Acute and chronic oxaliplatin-induced peripheral neuropathy were evaluated in patients with colon cancer receiving adjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin) in a previously reported calcium/magnesium neuropathy prevention trial (Loprinzi JCO 2013). Acute neuropathy was assessed using daily questionnaires for 6 days starting with each cycle of FOLFOX. Chronic neurotoxicity was assessed using the EORTC QLQ-CIPN20 tool before each dose of oxaliplatin and at 1, 3, 6, 12, and 18 months after chemotherapy. Results: 89% of patients (308/346) had at least one acute neuropathy symptom (Sx) with the first cycle of FOLFOX: sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute neuropathy Sx occurred within a day after oxaliplatin, peaked at day 3, then improved. These Sxs, however, did not resolve completely between treatments and were about twice as severe in cycles 2-12, than in cycle 1. Cycle 1 acute neuropathy Sx severity predicted acute Sx severity in subsequent cycles. Regarding the chronic neurotoxicity, tingling was the most severe Sx (1.91 out of 1-4), followed by numbness (1.72), and then pain (1.28). During chemotherapy, hand Sxs (1.70) were more prominent than feet Sxs (1.57). Following chemotherapy completion, sensory Sxs initially continued to worsen, on average, with improvement beginning approximately 3 months post-chemotherapy. By 18 months, residual numbness/tingling was more severe in feet than in hands. Patients with more severe acute neuropathy during the first cycle of therapy had more chronic sensory neurotoxicity (P<0.0001). Conclusions: Acute oxaliplatin-associated neuropathy Sxs do not completely resolve between treatment cycles and are only half as severe on the first cycle compared with subsequent cycles. There is a correlation between the severity of acute and chronic neuropathy. Hand Sxs are more severe during therapy, while feet symptoms become more prominent during follow up. Clinical trial information: NCT01099449.