Background Osteopontin (OPN) mRNA is highly expressed in atherosclerotic plaques and plasma OPN levels are high in patients with coronary artery disease and in those with restenosis. OPN-overexpressing transgenic mice show markedly increased neointimal formation after arterial injury. Methods and Results The prognostic significance of the preprocedural plasma OPN level was investigated in 130 patients undergoing percutaneous coronary intervention (PCI). Patients were followed up for restenosis and major adverse cardiovascular events (MACE). At 7±3 months after PCI, angiography was performed again in 91 patients, of whom 40 had restenosis. Between patients with and without restenosis, OPN (492±200 vs 482±224 ng/ml) and C-reactive protein (CRP: 0.78 vs 0.70 mg/L) levels did not differ. During a 3-year follow-up, MACE occurred in 21 patients, who had higher OPN (586±230 vs 438±195 ng/ml) and CRP (1.30 vs 0.70 mg/L) levels than those without MACE (P<0.005). Both OPN and CRP levels were independent predictors for MACE. Hazard ratios for MACE were 1.3 (95% confidence interval (CI) 1.1-1.5) for a 100 ng/ml increase in OPN and 3.6 (95%CI 1.4-9.3) for CRP >1.0 mg/L. Conclusions In patients undergoing PCI, the preprocedural OPN and CRP levels are independent predictors for further cardiovascular events, but not for restenosis. (Circ J 2009; 73: 152 - 157)