Although intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) play a relevant role in atherosclerosis, little is known about the prognostic impact of their soluble forms (s) in patients with peripheral arterial disease (PAD). The aim of this prospective study was to verify whether plasma levels of sICAM-1 and sVCAM-1 predict cardiovascular risk in PAD, and improve the prognostic value of the ankle/brachial index (ABI) alone. Accordingly, plasma levels of sICAM-1 and sVCAM-1, and the ABI were measured in 75 PAD patients who were monitored for a mean of 24+/-13 months. Twenty-two (29.3%) patients had a cardiovascular event (15 coronary, 3 cerebrovascular and 4 peripheral events). Plasma levels of sVCAM-1 were 618+/-258 ng/mL in patients with and 496+/-164 ng/mL in those without an event (p=0.016). The corresponding sICAM-1 values were 344+/-239 ng/mL and 275+/-99 ng/mL (p=0.079). The cardiovascular event rate was higher in patients with sVCAM-1 levels above the median than in those with sVCAM-1 below the median (p=0.0027 by log rank test). Independent predictors of events were sVCAM-1 levels above the median (p=0.005) and an ABI below the median (p=0.001). Amongst patients with ABI below the median, the occurrence of sVCAM-1 above the median was associated with a 3.4-fold increase in risk (95% CI 1.308 to 9.573, p=0.013). In conclusion, increased plasma levels of sVCAM-1 have a negative prognostic impact in PAD and improve the predictive value of ABI, which is currently the most powerful risk indicator in these patients.