BACKGROUND AND PURPOSE: Venous thromboembolism extended prophylaxis after inflammatory bowel disease surgery remains controversial. The purpose of this study was to evaluate if adopting an aspirin-based prophylaxis strategy may address current cost-effectiveness limitations. METHODS: A decision analysis model was used to compare costs and outcomes of a reference case patient undergoing inflammatory bowel disease-associated colorectal surgery considered for post-discharge thromboembolism prophylaxis. Low-dose aspirin was compared to an enoxaparin regimen as well as no prophylaxis. Source estimates were obtained from aggregated existing literature. Secondary analysis included out-of-pocket costs. A 10,000-simulation Monte Carlo probabilistic sensitivity analysis accounted for uncertainty in model estimates. RESULTS: An enoxaparin-based regimen compared to aspirin demonstrated an unfavorable incremental cost-effectiveness ratio of $908,268 per quality-adjusted life year. Sensitivity analysis supported this finding in > 75% of simulated cases; scenarios favoring enoxaparin included those with > 4% post-discharge event rates. Aspirin versus no prophylaxis demonstrated a favorable ratio of $106,601 per quality-adjusted life year. Findings were vulnerable to a post-discharge thromboembolism rate < 1%, aspirin-associated bleeding rate > 1%, median hospital costs of bleeding > 3 x , and decreased efficacy of aspirin (RR > 0.75). The average out-of-pocket cost of choosing an aspirin ePpx strategy increased by $54 per patient versus $708 per patient with enoxaparin. CONCLUSIONS: Low-dose aspirin extended prophylaxis following inflammatory bowel disease surgery has a favorable cost-safety profile and may be an attractive alternative approach.