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Experimental data suggest that aspirin-induced platelet inhibition may retard growth of abdominal aortic aneurysms. In this article, whether low-dose aspirin use is associated with reduced aneurysm progression and subsequent need for surgery is examined. In this observational cohort study within a screening trial, 148 patients with small aneurysms (maximum diameter 30–48 mm) annually are followed. Patients were referred for surgery when the aneurysmal diameter exceeded 50 mm. Median follow-up time was 6.6 years. Among patients whose abdominal aortic aneurysms were initially 40 to 49 mm in size, the abdominal aortic aneurysm expansion rate for low-dose aspirin users compared with nonusers was 2.92 mm/y versus 5.18 mm/y (difference 2.27 mm/y, 95% CI, 0.42–4.11). No difference in expansion rates and risk ratios for operative repair was found for patients with abdominal aortic aneurysms < 40 mm. For medium-sized abdominal aortic aneurysms, low-dose aspirin may prevent abdominal aortic aneurysm growth and need for subsequent repair, but residual confounding cannot be excluded.