Background: Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancerrelated mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. Methods: We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. Results: High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] ¼ 2.77, 95% confidence interval [CI] ¼ 1.90 to 4.02, P trend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR ¼ 1.75, 95% CI ¼ 1.22 to 2.51, P trend ¼ .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR ¼ 3.66, 95% CI ¼ 1.88 to 7.12, P interaction ¼ .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. Conclusions: Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted. Postdiagnosis lifestyle behaviors, including diet and physical activity, may be important risk factors for cancer recurrence and death in colon cancer patients (1-3). The exact mechanisms through which these factors influence outcomes are unknown, but epidemiological evidence suggests that insulin may play a role (4,5). Moreover, insulin signaling involves downstream pathways that are relevant for colon cancer pathogenesis and response to treatment (eg, KRAS/NRAS, BRAF, PIK3CA) (6,7). Insulin secretion is strongly influenced by diet, with carbohydrate-rich diets inducing postprandial hyperinsulinemia (8,9). Dietary glycemic load-an indicator of the body's plasma glucose response to different foods-has been