Background & Aims: Two separate decisions must be made for the management of patients with resected stage II/III colon cancer: whether to begin adjuvant chemotherapy and whether patients should be included in a follow-up protocol consisting of regular monitoring of carcinoembryonic antigen level and of colonoscopy and imaging. The standard management for these patients is adjuvant chemotherapy for stage III patients and follow-up for stage II/III patients with resected colon cancer. Methods: Decision analysis was used to compare the effectiveness (5-year survival rate) and cost-effectiveness ratio of 7 strategies of treatment and follow-up. Results: The most cost-effective strategies were adjuvant chemotherapy for all patients with stage II/III resected colon cancer, with either no follow-up or follow-up only for patients aged less than 75 years with a seric preoperative carcinoembryonic antigen level of >5 ng/mL (5-year survival, 62.3% or 62.7%; cost per surviving patient, $8254 or $8657, respectively). The order of efficacy of the strategies was insensitive to changes in the values of the studied variables. The method of follow-up does little to improve 5-year survival but adds substantial cost. Conclusions: The current standard strategy may not be the most cost-effective strategy for the management of patients with resected colon cancer. GASTROENTEROLOGY 1999;117:784-793