Background: Aspirin chemoprevention combined with colonoscopy screening is not cost-effective for the general population. However, the cost-effectiveness of aspirin in individuals with prior adenoma resection has not been evaluated. Aim: To evaluate the cost-effectiveness of aspirin chemoprevention alone and in combination with colonoscopy surveillance in patients with prior adenoma resection. Methods: A model of the natural history of individuals with a history of endoscopic polypectomy was constructed. Four strategies were compared: (i) no intervention, (ii) routine colonoscopy surveillance, (iii) aspirin chemoprevention alone, and (iv) aspirin therapy combined with colonoscopy. Results: Compared with no intervention, all other strategies were more costly but were associated with gains in years of life saved. Aspirin chemoprevention alone was associated with a gain of 0.0092 years, whereas routine colonoscopic surveillance and combination strategy were associated with further gains in years of life saved (0.0124 and 0.0138 years, respectively). Compared with no intervention, the incremental cost-effectiveness ratio of routine colonoscopy surveillance was $78 226 per year of life saved, and the incremental cost-effectiveness ratio of combination aspirin and colonoscopy was $60 942 per year of life saved. Conclusion: Aspirin chemoprevention combined with colonoscopic surveillance in post-polypectomy patients may be considered a cost-effective strategy. © 2007 The Authors.