Background: Cell therapy with endothelial progenitor cells (EPCs) is an emerging therapeutic option to promote angiogenesis or endothelial repair. While the release of angiogenic paracrine factors is known to contribute to their therapeutic effect, little is known about their release of pro-inflammatory factors and expression of pro-inflammatory adhesion molecules. Methods: "Early" EPCs and "late" EPCs were isolated from human peripheral blood and their release of chemokines and thrombo-inflammatory mediators as well as their expression of the pro-inflammatory adhesion molecules was assessed at baseline and with stimulation. The effect of Simvastatin on Monocyte Chemoattractant Protein-1 (MCP-1) secretion by "late" EPCs from patients with vascular disease was also evaluated. Results: All groups of EPCs released chemokines and thrombo-inflammatory mediators. "Early" EPCs primarily released thrombo-inflammatory mediators such as Tissue Factor (0.5±0.1 ng/million cells, p<0.05), while adult "late" EPCs primarily released chemokines such as MCP-1 (287±98 ng/million cells, p<0.05). Stimulation with TNF-alpha augmented their expression of the pro-inflammatory adhesion molecules and paracrine factors by all EPC subtypes. The release of MCP-1 by "late" EPCs was markedly reduced by Simvastatin treatment of the cells. Conclusions: All EPC subtypes expressed pro-inflammatory paracrine factors and adhesion molecules involved in atherosclerosis. Future clinical studies should therefore not only assess the efficacy of EPCs but also monitor inflammatory activation following EPC transplantation in patients. Pharmacologic modulation of EPCs before and after transplantation may represent a novel approach to improve their safety.