Plasminogen activator inhibitor 1 (PAI-1), the primary inhibitor of fibrinolysis and C-reactive protein (CRP), is a predictor of myocardial infarction. Both are upregulated by tumor necrosis factor-alpha (TNF-α) within the obese population. This pilot study tested the hypothesis that TNF-α blockade with pentoxifylline lowers PAI-1 and high-sensitivity CRP (hsCRP) in obese individuals. Twenty participants were treated with pentoxifylline for 8 weeks. A proportional odds model was used to compare the change in PAI-1 and CRP in the pentoxifylline and placebo groups. Plasminogen activator inhibitor 1, but not hsCRP levels, decreased over the 8-week period of the study (P = .025 and P = NS). There was significant dropout of participants due to drug tolerability. These findings suggest that these markers of cardiovascular risk are differentially regulated in obesity and that PAI-1 levels can be reduced by pentoxifylline in this population.