Although the mechanism whereby non-steroidal anti-inflammatory drugs may reduce abdominal aortic aneurysm (AAA) development is unknown, one potential route is via inhibition of the cyclooxygenase (COX) enzyme. Despite the fact that evidence from animal models suggests a role for the COX-2 isoform in promotion of AAA development, only very limited data exist on COX-2 expression in human AAAs. Semiquantitative immunohistochemistry for COX-2 was performed on a series of formalin-fixed, paraffin-embedded human AAAs (n = 49). Associated clinicopathological data, including the degree of inflammatory cell infiltration and neorevascularization, were obtained. COX-2 protein was detected in 46 of 49 (94%) human AAAs. Expression of COX-2 protein varied widely between AAAs. COX-2 protein localized to cells in the inflammatory infiltrate with a morphology characteristic of macrophages. COX-2 expression increased with the extent of inflammatory cell infiltration (P < 0.001) and with the degree of AAA neorevascularization (P < 0.001). Logistic regression analysis identified neorevascularization (P < 0.001) as the only significant independent predictor of COX-2 positivity in human AAAs. COX-2 protein is present at increased levels in the majority of human AAAs and is expressed by mononuclear cells in the inflammatory cell infiltrate. Promotion of angiogenesis by COX-2 may play a role in AAA development.