Objective: This study was conducted to determine the costs and comparative cost-effectiveness of two methods of abdominal aortic aneurysm (AAA) repair in the Open Versus Endovascular Repair (OVER) Veterans Affairs (VA) Cooperative Study, a multicenter randomized trial of 881 patients. Methods: The primary outcomes of this analysis were mean total health care cost per life-year and per quality-adjusted life-year (QALY) from randomization to 2 years after. QALYs were calculated from EuroQol (EQ)-5D questionnaires collected at baseline and annually. Health care utilization data were obtained directly from patients and from national VA and Medicare data sources. VA costs were obtained from national VA sources using methods previously developed by the VA Health Economics Resource Center. Costs for non-VA care were determined from Medicare claims data or billing data from the patient's health care providers. Results: After 2 years of follow-up, mean life-years were 1.78 in the endovascular repair group and 1.74 in the open repair group (difference, 0.04; 95% confidence interval [CI], −0.03 to 0.09; P = .29). Mean QALYs were 1.462 in the endovascular group and 1.461 in the open group (difference adjusting for baseline EQ-5D score, 0.006; 95% CI, −0.038 to 0.052; P = .78). Mean graft costs were higher in the endovascular group ($14,052 vs $1363; P < .001), but length of stay was shorter (5.0 vs 10.5 days; P < .001), resulting in a lower mean cost of the hospital admission for the AAA procedure in the endovascular repair group of $37,068 vs $42,970 (difference, –$5901; 95% CI, –$12,135 to –$821; P = .04). After 2 years, total health care costs remained lower in the endovascular group, but the difference was no longer significant (–$5019; 95% CI, –$16,720 to $4928; P = .35). The probability of endovascular repair being less costly and more effective was 70.9% for life-years and 51.4% for QALYs. Conclusions: In this multicenter randomized trial, endovascular AAA repair resulted in lower cost and better survival than open repair after the initial hospitalization for repair; but after 2 years, survival, quality of life, and costs were not significantly different between the two treatments.