Obesity is associated with increased morbidity and mortality from atherosclerotic disease. Nontraditional cardiovascular risk factors such as C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in obese subjects and weight loss is associated with an attenuation of these risk factors. Matrix metalloproteinase-9 (MMP-9) has been linked to plaque rupture, and is, thus, a candidate marker of future myocardial events. The aim of this study was to determine the influence of weight loss on MMP-9 plasma concentrations. CRP, IL-6 and MMP-9 were analyzed from samples of 45 morbidly obese, middle-aged women before gastric banding and 1 y postsurgical treatment in this prospective study. The body mass index (BMI) of subjects decreased from 42.5+/-4.9 to 32.3+/-5.3 kg/m(2) 1 y after gastric banding. In parallel, both MMP-9 and CRP were reduced by 23 and 41%, respectively. A positive relationship was found between BMI and MMP-9 (r=0.312, P<0.05), and between CRP and IL-6 (r=0.508, P<0.05), whereas no correlation was found between CRP and MMP-9. We conclude that weight loss is associated with a pronounced decrease in the nontraditional cardiovascular risk markers MMP-9 and CRP, which could indicate future beneficial effects of weight loss on the cardiovascular risk in weight loosing subjects.