In-stent restenosis represents the major limitation of percutaneous coronary revascularization. The underlying neointimal hyperplasia mainly consists of smooth muscle cells (SMCs), which can be derived from bone marrow cells. We hypothesized that changes in the peripheral progenitor cell counts after coronary stenting may predict the development of restenosis. We prospectively studied men with atherosclerotic coronary artery disease who had undergone successful elective stenting of solitary target lesions (n = 17). Peripheral blood samples were drawn at baseline (before stenting) and 1 day after stenting. The CD34+ cell count was determined by flow cytometry. Follow-up quantitative coronary angiography was performed after 8.1 +/- 2.6 months. Except for longer primary lesions in patients with angiographic restenosis, no significant differences in patient and lesion characteristics were seen. The rate of restenosis (75% vs 11%, p = 0.015) and the extent of diameter stenosis at follow-up (56.9 +/- 26.9% vs 26.5 +/- 16.5%, p = 0.012) were higher in patients with a postprocedural increase in CD34+ cells than in those with a decrease in CD34+ cells. Postprocedural CD34+ cell counts were increased in patients with restenosis but decreased in those without restenosis (p = 0.002). A robust correlation was seen between the change in CD34+ cells and late lumen loss (r = 0.65, p <0.005). In a multivariate regression model, the change in CD34+ cells, lesion length, and preprocedural minimal lumen diameter independently predicted for late lumen loss. In conclusion, an increase in circulating CD34+ cells after coronary stenting constitutes an independent risk factor predicting in-stent restenosis and may be suggestive of their involvement in neointimal hyperplasia.